Spondylitis Association of America

Potential "Patch" for AS

Posted By: PainintheAS

Potential "Patch" for AS - 05/23/19 03:18 AM

Hi, fellow Spondylonians!

I have been suffering from varying levels of disease related to the HLA-B27 gene for the last 10+ years. I have always had a sensitive gut, felt more muscle pain than my friends after sports, had lethargy randomly, and experienced pain in my joints randomly that feels like a dull sting/ache up to a sharp poke in various "cartilage" formations in my body. I never knew why I had all these things. I have actually acquired a few different infections throughout my early 20's and they have contributed to an upregulation of what originally appeared to be "gout," but was actually Reactive Arthritis. I am now 33, and have recently traveled to Mexico within the last year and a half and happened to contract water/food-borne pathogens. The infection took a few months to eradicate, and I believe in doing so it upregulated my autoimmunity a step further, either by the specific pathogen or by me to try to kill it with antimicrobials I opened the door to Klebsiella-like invaders, which caused the standard pain in the spine alongside some episcleritis and ringing in my ears (possibly Ménière's disease.) Being the epic nerd I am (though a well-rounded one) and majoring in physics, I consider myself a citizen scientist. I have read these, and other, forums multiple times over in order to try and gain some insight into treatment and management of the various disease states associated with AS/HLA-B27, such as dietary changes and medications.

It was clear to me at around 16-18 that I had a problem in my guts. Any time my guts would hurt, other parts of me would ache, particularly my upper-midback behind my left shoulder blade, as well as my midback. I theorized then that I had a bacterial imbalance that needed to be addressed. Unfortunately, ALL my endeavors were mainly fruitless, but I wouldn't find out why until this month at the age of 33. It would be because my gene (HLA-B27) predisposes you to an aberrant microbiome through altered inflammation pathways, which I won't get into here. Any research on the current state of affairs on google will show you that this is the case in HLA-B27+ individuals. I only found out I was HLA-B27+ about 6 months ago, and it was overwhelming to realize nothing I ever did was going to matter because my genetics had been the cause of the dysfunction this WHOLE TIME. After about 1 week of feeling mildly depressed, I buckled down and went FULL NERD CITIZEN SCIENTIST mode. I am here today to share with you what I believe may be the BEST answer we currently have for AS and how to manage your AS until a cure is found. I am so sorry for those individuals out there whose bodies have been ravaged so badly by this disease that the damage itself causes so much pain, that even after stopping the disease...you will still be in a lot of pain. My heart goes out to you. I started this research because of reading on these forums what some people go through and decided I would NOT accept getting to that phase and that there MUST be something I could do (whether that was true or not is irrelevant.) Here you go:

1) The disease is not only related to the microbiome/gut but also periodontal in nature (for some.)

Periodontal Causes

Standard/Common Klebsiella Theory

Link Between Dietary Carbs + Polysaccharides in Bacteria and Immune Complexes Formed

2) The offenses to the gut eventually lead to chronic inflammation and aberrant cytokine expression (mediated by interleukins which are modulated by intestinal bacteria)

Gut Microbiome Imbalance Mediated by HLA-B27 and Associated Upregulation of Cytokine Expression

I have TONS and TONS more articles I've read that I could post here but this set of 4 gets it done nice and concisely, and was my launching point for treating myself...particularly the article in section 2. I will explain in detail.

--

What was discovered was that cytokines are misregulated (upregulated) because the bacteria that are allowed to thrive in the guts of HLA-B27+ people have a skewed firmicutes/bacteroidetes ratio. There are other known oddities compared to healthy controls, but this is a constant finding. These particular bacteria were found to promote the production of interleukins, specifically the ones related to cytokine production, NF-κB, TNFα, etc. This is why science has so far been focusing on drugs that are IL-17/IL-17A blockers/auto-antibodies as well as some dealing with IL-6. These drugs would stop the downstream upregulation of cytokines that promote inflammation. However, THIS poses a huge problem. You are basically blunting your immune response, and thus opening yourself up to increased infection/cancer risks, etc. To me, this type of solution is barbarism. This is NOT how you treat a disease that is related to gut microbiota.

However, that very same study demonstrates that an antibiotic (Rifaximin) was used, as it is not well-absorbed by the body, but has both anti-inflammatory and broad-spectrum anti-bacterial effects. Because it is not well absorbed by the body, most of the action of the drug is maintained in the intestines (this is a huge plus) as well as 98% percent is excreted in the feces (Link) Rifamycin (from the previous link) actually does a slightly better job with less colonic cell toxicity, but at the time I read the links from sections 1 and 2 I hadn't read this yet; however, it doesn't matter for short-term dosing. The Rifaximin/Rifamycin drugs also upregulate a few other metabolic pathways related to detoxification. However, and most importantly, Rifaximin increases tight-junction protein synthesis! This means it will seal up them LEAKY GUTS! Once the guts are sealed, then the affronts to the immune system will begin to decrease, which will lead to less inflammation, which will lead to less bone deformation from cytokine upregulation. Not only that, but the drug also returned the aforementioned ratios of bacteria to a more normal level. I mean, COME ON FOLKS, this is about as good as it gets. Seal the gut, restore the bacteria to a more normal distribution, reduce interleukins and cytokines to more normal levels, and...DRUM ROLL...it halted the progression of the disease (in mice, granted.)

SO...we have some pretty compelling evidence that this is the bee's knees, my friends. It will not shut down your immune system in ways that open you up to infection, in fact, it will normalize your immune system. Your intestines will begin to seal, and in doing so...you can probably eat more food that you enjoy again, including them pesky carbs. The list of reasons to take this over biologics and TNFα blockers goes on and on, which I vetoed that method for myself because I just saw too many problems with it.

I decided to get this drug for myself, and while I am only 2 days into using it (2nd pill on the 2nd day) I have to say...whoa. By the 2nd pill on the first day, I was feeling "lighter" and less burdened. The cytokine activity was likely lower in me due to the immediate anti-inflammatory effects of the drug. I was smiling, being goofy, and more like my normal self. Not to mention, I had just had an AS flare in my lower back a few days prior and was bed-ridden. I had been applying the unhelpful lidocaine patches given to me by the rheumatologist, which I knew would basically do nothing but tried anyway. Not to mention, I got out of bed at end of day 1 and went to my couch...still in mild pain of course...and watched a full movie in the recliner seat of my couch. I couldn't even sit for more than 5 minutes without ridiculous pain before. Today, the pain is even less. Oh, not to mention the Reactive Arthritis that has been ongoing for quite some time, as well as general inflammation, caused me to recently have a severe bucket-handle tear of my meniscus (90%.) I just had surgery about 2 weeks ago and have also been having a hell of a time with that, but today I got up and walked around without my crutches (albeit looking stupid) I felt stronger and more capable with less inflammation pain...so I just went for it. I am going to continue this drug for a full month, and then I am going to try Rifamycin for an additional week to see if it makes me feel even better. From one of the studies I read, Rifamycin has better regulation of certain cellular pathways for inflammation and it also stimulates cell-turnover/repair genes in the intestines, making it a powerful tool for further sealing up them guts.

I really hope that this has helped, or does help, someone. For me, this has given me hope again as I have been bedridden from both AS + surgery pain, plus I was unable to walk for 2 months because everyone wanted to remove my meniscus until I found Dr. Webber in Los Angeles, who is insanely well rated and accomplished and performed a repair...which was successful! So, I've been in sorry shape for a while, which gave me time to buckle down and get this research done, and to take the risk on Rifaximin. Please note that if you are allergic to Rifaximin, there is another antibiotic listed in the studies above (moxifloxacin) that has been very effective. You can search for separate studies for that, and you'll find it. I had side effects that were mild on day one, but I think that's because the gut is leaky, and it leaks into the bloodstream. The effects were less on day two. The first day, I had an elevated heart rate (around 88 BPM.) The second day I am around 72-75 BPM after a meal and taking Rifaximin.

If anyone wishes to discuss this with me, I am more than happy to provide links to other things I've found through my research, the list is about 50-70 links or more and I have spent around 400+ hours reading. I feel very well-read on these topics and that I have a pretty good understanding of the general way this disease comes about and begins to take shape over time.

(Special Notes: If you also have the periodontal infections, Rifaximin alone will not stop the progression of your disease. There was another study looking at using Rifaximin in oral injections into the gums in order to stop the disease, and it looked promising, but I think there are also other drugs to be used for injection into the gum gaps and mouthwashes that can maintain effects. Please get your GUT and your ORAL microbiota checked. If you are HLA-B27+, you can be assured your microbiome is whacked, so just check the oral microbiota and start Rifaximin anyway. The bacterial composition of the gut needs to be normalized for the cytokine production to return to normal levels. Also, another recent study found that HLA-B27 did NOT change the severity of AS disease, only the quickness of its onset, so all of you NON HLA-B27 people who have AS, you still likely have oral or gut related damage/imbalance that took longer to form, since you are not predisposed to high levels of inflammation in the gut)

Good luck everyone!

Also: DO NOT TAKE RIFAXIMIN FOR MORE THAN 3 MONTHS! YOU NEED TO CYCLE THIS DRUG OTHERWISE YOU RUN THE RISK OF FATTY LIVER Fatty Liver Issues for Long-Term Use of Rifaximin This is related to those other metabolic pathways I mentioned that Rifaximin and Rifamycin upregulate. In this case, it's triglycerides that get increasingly absorbed due to upregulated metabolization pathways. This is not an issue after 1 month of use. I recommend 1 month, then come back and start taking Rifaximin again as symptoms begin to return.

I am not a doctor, this is not medical advice, and this is my theory on how one can help themselves stave off progressive damage without blunting their immune system. I am currently doing this and feeling rapidly better. Please note that I am reporting my thoughts and experiment with this treatment and if you do so, you do so at your own risk...please consult a doctor first (though they will probably tell you this drug is not even indicated for treatment of this disease, which its not because this article for its use in AS was released in March of 2019. Have fun waiting years and years for it to be approved.) If you wish to get this drug under the supervision of a doctor, the best way would be to prove you have SIBO, which you might have given your microbiome is out of balance. Or IBS-D is another way. Cheers!
Posted By: DadCue

Re: Potential "Patch" for AS - 05/23/19 11:26 AM

What about the uveitis ... how does that factor into all this?
Posted By: RAHMBA

Re: Potential "Patch" for AS - 05/23/19 06:11 PM

Thank you for the post PainintheAS.

I see that you are in the LA area. Please come to the Los Angeles Education/Support Group on June 9th from 2pm - 4pm. I would really like to meet you. https://www.spondylitis.org/Community/Support-Groups/Los-Angeles
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/23/19 06:16 PM

So, I only developed episcleritis (luckily) after my visit to Mexico and acquiring the infection. All of these disease states (IBS/IBD, Uveitis/Scleritis, Reactive Arthritis, Ménière's, and AS) are related to the body attacking collagen, from what I have researched. The best evidence for this is the Klebsiella theory. It also turns out that a few other bacteria, which I believe are mentioned in the link I gave above, such as: Yersinia

The first paper I ever read described the link between toxins created by bacteria being injected into rabbits which immediately caused uveitis. Link I realized that ALL of these things were related to bacteria, the way they reprogram our immune system, and specific mimicry (a peptide from them that our immune system recognizes as an invader and attacks but is also is similar to compounds of our body elsewhere.)

More recently, this was done to explain more clearly why there is a link between AS and uvetis. However, the main idea is the same: bacteria, mimicry, peptides, and a reactivity to those peptides.

The take away is that the gut leaks, the leaking allows things to enter the blood stream that normally should not be there at all. Once those things are there, the immune system mounts a defense, and that is totally normal. However, the things that it is mounting defense against would normally never be in the blood but only in the gut and therefore the attack it launches can have system-wide effects. My current belief is that sealing the gut is a NECESSITY or else these type of reactions will continue to occur.

It is of considerable mention that HEALTHY animals can have uveitis induced by injecting into their bloodstream various endotoxins or peptides produced by bacteria. So why did they never get sick before? They either a) never had the bacteria to begin with, or b) their gut never allowed it to leak into the blood. Given that all animals and people share many common environmental factors like food, housing, geographic location, etc. ... it would seem that the first explanation is just not the correct explanation. We return to the fact that healthy animals have an intact gut membrane that doesn't allow things into their bloodstreams in order to produce the uveitis.

It was mentioned in these papers that oral tolerance (feeding the peptides orally that the body is reacting to) severely decreased severity of reaction. You might want to go to an immunologist/allergist and present some of these papers or ask if you can find out what antibodies your body is creating (IgA usually) as they are a marker of fighting infection. The elevated levels of antibodies to Klebsiella is common, and in the oral infection route there will be the others listed in the paper I shared. We could probably all dig down and find out what peptide fragments these particular microbes are presenting to our immune system (through other papers) and see if someone has experimented with oral tolerance in them as well.

Main take home statement will always be: HEAL and SEAL them guts

Hope this helped!
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/23/19 06:19 PM

Originally Posted by RAHMBA
Thank you for the post PainintheAS.

I see that you are in the LA area. Please come to the Los Angeles Education/Support Group on June 9th from 2pm - 4pm. I would really like to meet you. https://www.spondylitis.org/Community/Support-Groups/Los-Angeles


I will try to make it! I am still recovering from my meniscal surgery, so my walking is limited still. It's too bad it's not the day after, because that's when I see my surgeon to get the "go ahead" to flex my leg more than 90 degrees. I will try to be there!
Posted By: Buddy

Re: Potential "Patch" for AS - 05/23/19 11:51 PM

I have been diagnosed with AS but do not have the HLA-B27 marker. I am 52 years old and started getting systems of AS in 2014. I have never been a big dentist goer but I do take care of my teeth. I never got cavities until my 30's then my mouth was a mess. I got it taken care of and went on with my life. Long story short my mouth was a slight mess again and have most of it taken care of. Just one more root canal. Soooo this all make a lot of sense now after reading your dissertation. Thank you for this and how many rheumatologist know about this? My doctor has done extensive tests on my gut but was looking for Crones or maybe this but she never asked or looked at my mouth.

Thanks Again PainintheAS
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/24/19 12:23 AM

Originally Posted by Buddy
I have been diagnosed with AS but do not have the HLA-B27 marker. I am 52 years old and started getting systems of AS in 2014. I have never been a big dentist goer but I do take care of my teeth. I never got cavities until my 30's then my mouth was a mess. I got it taken care of and went on with my life. Long story short my mouth was a slight mess again and have most of it taken care of. Just one more root canal. Soooo this all makes a lot of sense now after reading your dissertation. Thank you for this and how many rheumatologists know about this? My doctor has done extensive tests on my gut but was looking for Crones or maybe this but she never asked or looked at my mouth.

Thanks Again PainintheAS


Unfortunately, many doctors don't stay current with things as they come into the fold of scientific understanding, or they call it a "prevailing theory" and dismiss it's validity because they believe they have some greater understanding from their institution, professors, or powers of logical deduction. The medical community often fails to even follow the "Hypocratic Oath," because (funny enough) they are hypocritical...they almost got it right by spelling. I have experienced people literally getting angry or frustrated with me because I have done the research and brought articles to the table with me. The problem here is that a true scientist (and medicine should be science, and doctors don't practice medicine...and drug companies are creating medicines but not practicing it) should remain open to all possible forms of presented arguments and then with the appropriate evidence make judgments or form new experiments. People all have chips on their shoulders, but I've got them in my bones...and they hurt...so I don't care what they think is reasonable or not...I'm going to find the truth one way or another.

The short answer is, not many know...and the ones that do just look at these things as "unproven theories." Problem is...that shouldn't matter...try treating it as true and see the effect. Oh...wait, they can't because the drug companies and insurance companies work together to put money in doctors' pockets in order to give you the drugs that are currently available. Anything outside that...not really gonna get them to entertain you, my friend. The only way that would be possible would be looking into more integrative medicine or naturopathic doctor who has roots in western medicine. Otherwise, be prepared for most doctors to get annoyed with you.

I hope you begin to feel better or are already starting to find relief somehow!
Posted By: DadCue

Re: Potential "Patch" for AS - 05/24/19 12:29 AM

This may not be pertinent to most and I have more or less moved on from the AS forum. I was diagnosed with reactive arthritis 25 years ago and HLA-B27+.

I had a rough time for 15 years with pain but uveitis lead me on Prednisone. Ten years ago the reactive arthritis diagnosis "morphed" into polymyalgia rheumatica and 10 mg prednisone was prescribed daily. Prednisone 10 mg daily seemed to alleviate the reactive arthritis symptoms and completely stopped uveitis.

Recently, a new rheumatologist wanted to spare the prednisone and prescribed Actemra for polymyalgia rheumatica. This treatment worked very well and I quickly tapered off prednisone for 5 weeks until the uveitis flared up after a 10 year hiatus and I'm back on 50 mg prednisone.

My impression is that people with AS consider prednisone "barbaric" but it has been a huge part of my life for 25 years. There's no need to go into any detailed response but I would be interested in trying RIFAXIMIN. This interests me because ground zero 25 years ago was probably traveler's diarrhea.

Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/24/19 02:00 AM

Originally Posted by DadCue
This may not be pertinent to most and I have more or less moved on from the AS forum. I was diagnosed with reactive arthritis 25 years ago and HLA-B27+.

I had a rough time for 15 years with pain but uveitis lead me on Prednisone. Ten years ago the reactive arthritis diagnosis "morphed" into polymyalgia rheumatica and 10 mg prednisone was prescribed daily. Prednisone 10 mg daily seemed to alleviate the reactive arthritis symptoms and completely stopped uveitis.

Recently, a new rheumatologist wanted to spare the prednisone and prescribed Actemra for polymyalgia rheumatica. This treatment worked very well and I quickly tapered off prednisone for 5 weeks until the uveitis flared up after a 10 year hiatus and I'm back on 50 mg prednisone.

My impression is that people with AS consider prednisone "barbaric" but it has been a huge part of my life for 25 years. There's no need to go into any detailed response but I would be interested in trying RIFAXIMIN. This interests me because ground zero 25 years ago was probably traveler's diarrhea.



I shall not analyze, but I too have ReA. Prednisone is just scary because it really messes with hormonal system. However, if you do try Rifaximin, please be careful not to stop your therapy because if you are incorrect about it being PURELY gastrointestinal (i.e. perhaps its also in your mouth/gums too) then you will flare up horrendously. But I am glad I was able to interest you in this new treatment option. Let me know what your endeavors are like trying to obtain coverage, etc.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/24/19 08:19 AM

I forgot to mention, I ran a biofilm protocol just 1 month before taking my Rifaximin course and it actually made me feel worse. This is logical to me as disrupting biofilms (which likely cover sections of extremely irritated and offended intestines) could expose areas of the gut that are weakened in integrity. These exposed sections are then going to leak into the bloodstream at an accelerated rate compared with a section that was covered by biofilm and leaked based on the activity of the bacterial colony within. I ended up stopping the protocol, doing a juice cleanse, which also didn't seem like a good idea for other similar reasons, and then started Rifaximin. Rifaximin and the tight-junction proteins it stimulates are exactly what seems to be needed in order to stop this issue from occurring.

It would seem to me that is possible that HLA-B27 individuals, with their skewed firmicutes/bacteroidetes ratio (fewer firmicutes in HLA-B27+ individuals,) likely produce far too little butyrate, one of the SFCA's. It is the firmicutes that produce butyrate, while the bacteroidetes that produce propionate and acetate. While all of these compounds are beneficial, I could imagine too much acetate (an anion formed from acetic acid) and too little butyrate could cause an environment where there is a high level of reactivity (due to higher negative charge flux in the colon from acetate) to the surrounding tissues without the energy (butyrate is colon cell energy) necessary for repair and structural integrity. Seems like this system is so finely tuned that deviations from this interplay have drastic consequences. It also seems not to matter as much exactly what type of bacterium exist, with a few exceptions, but that they need to belong to either the class of firmicutes or bacteroidetes, and their ratios need to be what they are in healthy controls.

Since those with HLA-B27 will have aberrant inflammation responses due to cytokine overexpression upon offense, with a predisposition for altered gut microbiota...this seems to me to put the nail in the coffin. It would explain why those with HLA-B27 would arrive at disease far quicker than those with AS and are negative for HLA-B27.

Article on Obesity (but also the roles of firmicutes and bacteroidetes)
Posted By: dan321

Re: Potential "Patch" for AS - 05/24/19 03:15 PM

Originally Posted by PainintheAS
I decided to get this drug for myself


Just wondering how you got the prescription for Rifaximin? Through a doctor? I was thinking to myself I'm not sure how I would even obtain this.

I have seen some others mention success with antibiotics over the years but they seem to be more on the fringe. I'd be interested to see how it goes for you after a longer period.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/24/19 07:29 PM

Originally Posted by dan321
Originally Posted by PainintheAS
I decided to get this drug for myself


Just wondering how you got the prescription for Rifaximin? Through a doctor? I was thinking to myself I'm not sure how I would even obtain this.

I have seen some others mention success with antibiotics over the years but they seem to be more on the fringe. I'd be interested to see how it goes for you after a longer period.


I mentioned some routes near the end of the post, which would be trying to demonstrate SIBO. It is also being approved for IBS, which many individuals with AS will have by nature of the disease.
Posted By: RAHMBA

Re: Potential "Patch" for AS - 05/24/19 08:15 PM

Wishing you a speedy recovery!

We've been meeting on a nearly monthly basis for years, so whenever you want to join, you are welcome :-)

kind regards,
Rich
Posted By: RAHMBA

Re: Potential "Patch" for AS - 05/24/19 08:29 PM

When looking for a cure, we encourage our researchers to explore and run studies.

Please consider:
Rifaximin has never been studied to treat AS. There is a high amount of conjecture. One persons unblinded results of two days of usage for a chronic condition is not something I would think any physician would recommend without more data.

I'm grateful that this forum is here for people to share experiences and ideas.
Posted By: RAHMBA

Re: Potential "Patch" for AS - 05/24/19 08:31 PM

Generally regarding antibiotics and spondylitis:

Prolonged and even short-term use of antibiotics can alter one’s microbiota, and in particular gut microbiota. Gut microbiota are implicated in the pathogenesis of spondyloarthritis, but it remains to be determined whether there is a particular shift one way or another, that is ‘good’ or ‘bad’ for SpA. It is also unclear as to whether changes in gut microbiota can trigger SpA, or whether SpA triggers changes in gut microbiota (or both). Prolonged courses of antibiotics can lead to many gastrointestinal problems and could make someone’s SpA worse, OR could make their SpA better. It’s just not clear.

I hope that helps.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/25/19 02:11 AM

Originally Posted by RAHMBA
When looking for a cure, we encourage our researchers to explore and run studies.

Please consider:
Rifaximin has never been studied to treat AS. There is a high amount of conjecture. One persons unblinded results of two days of usage for a chronic condition is not something I would think any physician would recommend without more data.

I'm grateful that this forum is here for people to share experiences and ideas.


The studies I referred to did use Rifaximin to treat AS, but only in mice so far. There are also studies I supplied where symptoms of AS were severely reduced using moxifloxacin in human patients with GREAT results. This already puts another tick on the side of "treat bacteria, reduce AS symptoms." (LINK)

Originally Posted by RAHMBA
Generally regarding antibiotics and spondylitis:

Prolonged and even short-term use of antibiotics can alter one’s microbiota, and in particular gut microbiota. Gut microbiota are implicated in the pathogenesis of spondyloarthritis, but it remains to be determined whether there is a particular shift one way or another, that is ‘good’ or ‘bad’ for SpA. It is also unclear as to whether changes in gut microbiota can trigger SpA, or whether SpA triggers changes in gut microbiota (or both). Prolonged courses of antibiotics can lead to many gastrointestinal problems and could make someone’s SpA worse, OR could make their SpA better. It’s just not clear.

I hope that helps.


I am pretty sure it was the papers I mentioned, or others I can find if not, that the bacterial shifts pre-dated the SpA. This was not just one experiment, this is well-documented in multiple experiments. Please, search for these findings and you will find them. The direct link between microbiota affecting the interleukin pathways, which then upregulated the cytokine expression is well-documented in them. I didn't make that up. While you are stating these things to be safe, I think what is more accurate is that "mainstream medicine" has not "accepted" these things as the truth, but the data backs them up in multiple studies already and that is why they keep getting funded...because there is merit in the idea. What I mean is that there is "repeatable" experimentation being done...and these repeated experiments find the same thing and multiple organizations/institutions/people keep funding these repeated experiments.

Also, in reply to this alteration of gut microbiota by taking antibiotics...yes it is true. However, at least that is exactly the target of the drug and you are intending to affect what you are affecting. How about all the drugs every single person on this forum takes to manage pain, such as NSAIDS, or others that take diabetes medications, etc. These are not intended to affect gut microbiomes, yet are prescibred and supposedly help people. (LINK) They have anti-microbial effects and even promote resistance to drugs. So, at least what I am proposing is EXACTLY the target it should be intending to affect. I'd suspect all these IL-17 and IL-6 drugs are also affecting the microbiome, since they modulate interleukin activity anyway.

Also, I am now on my 4th day and went to physical therapy. I have NEVER been able to sit in a seated position and do my exercises without frequent breaks because I am in so much pain. Today, I did all exercises without even needed to stand up and "shake it off." I walked into therapy without crutches today, and they said to me, "Who is this guy? You are like a completely different person." Again, anecdotal, but it lines up with what I'll reference next.

I am not the only person who has used Rifaximin, however, I am the only one to put all the pieces together for everyone. This person
(LINK) also had the same experience and was, and I quote, "afraid to stop taking Rifaximin," because of how her pain completely went away while on it. Her doc even called in and agreed to refill her script! (Dig deeper into that post and you will see that Rifaximin only stays in the intestines and is not well absorbed, as I discuss below. Also, another poster there talks about how amazing Rifaximin is in its ability to help with AS, and he claims it is "the best for AS." So, this brings the count from 1, now to 3, and these are people who have done more than my few days of dosing.)

I am not trying to be a pest, but medicine often moves slower than science, which often moves too slowly as well, when it need not and people get harmed or end up incurring "damage in wait." It is already accepted that "healthy people" have a VERY characteristic ratio of the different types of bacteria in their intestines performing similar tasks (though they may be different specific species, they are of the same class)...this is accepted and used as a clinical diagnostic standard. Ask companies that doctors use to assess their patients, like Genova Diagnostics...they will literally tell you what bacteria and what ratios are normal in healthy people because they are paid to know and collect this data. I can even provide my PDF's of my stool samples that show EXACTLY the same imbalance in firmicutes to bacteroidetes ratios that the mice in the first article I ever submitted for Rifaximin usage had. The mice transfected with HLA-B27 develop a disease progression which mirrors mine? This cannot just be due to coincidence. The chance of that being coincidence alone is astronomically low. It was also noted that Rifaximin alters gut microbiota towards ACCEPTED ratios of these bacteria, which is why it is now being prescribed for IBS, not just SIBO and HE. Rifaximin is also one of the safest of all antibiotics because it is not absorbed by the body. It only acts in the intestines because of this lack of absorption,(LINK), so for all the other people taking rounds of antibiotics anyway, this would still be safer than ALL of those in most cases (you are not allergic to Rifaximin.) I have taken antibiotics before and they all make me feel like garbage...this is THE ONLY ONE that I haven't felt really anything other than slightly elevated heart rate on day one. In fact, I am feeling so good I am smiling all day and becoming happier and more energetic.

I am just providing facts from papers that demonstrate, repeatedly, that gut microbiota shifts occur, and more recently they are reporting that it occurs BEFORE SpA. If it was the other way around then, "mice raised in germ-free environments don't develop SpA" (LINK) wouldn't make sense. It is the introduction to bacteria that causes the disease progression. Even if it WERE the other way, then you still need to treat bacteria being out of whack, to begin with, because SpA's got them out of whack. So fixing them at least addresses a problem...

Also, yes now it's more than just me experiencing success with this course of action for treating AS. The other methods of treating (interrupting communication between your body and your interleukin signaling) are far more dangerous, which is why people get infections, cancer, or even die from those treatment methods. If altering gut microbiota was a huge huge risky deal, people would be reporting tons more issues with probiotic supplements than they do. I have not really heard of people dying from probiotic usage, but Humira directly lists death as a possible side-effect. I am being extremely reasonable in deciding to attack the bacterial aspect of this disease due to both its safety profile and the logic behind it.

Lastly, each of the people on the forum who have replied to my post so far, including me, have all stated that some sort of gut or oral thing had happened to them before their disease started, or occurred right as the disease started. Putting this many pieces together, that all fit well with scientific evidence and all point to the microbiome, it would literally be one chance in a billion that these relationships were due to chance. I definitely ended my first post by stating that these were my opinions and that if people chose to follow suit, they did so at their own risk. I even detailed and outlined the risks associated with Rifaximin usage and dosing. Given all that, it is still my opinion that this is the safest and most well-targeted option currently out there for management of this disease, as well as potentially the best.
Posted By: DadCue

Re: Potential "Patch" for AS - 05/26/19 11:07 AM

I have no problem with what you are suggesting. I have read similar accounts of antibiotic therapy being used to treat reactive arthritis. I can easily envision an enteric infection causing an acute onset of reactive arthritis. The problem on this forum is that---if you haven't been diagnosed with AS and not taking a biologic, then you are in the wrong forum. It's not that I was treated badly ... I just felt I didn't fit i in. Especially since, I have been taking prednisone for years.

I would have a similar problem convincing my doctor to prescribe Rifaximin since I must have an iron stomach because I never have had any bowel issues except twice. The first time was 25 years ago at the onset of reactive arthritis. The second time, was a presumed case of norovirus and I found myself in an ICU. It sounds like you are suggesting the purpose of Rifaxmin is solely to "seal the gut" and not to treat any sort of infection. I can't help thinking that something has colonized in there that shouldn't have and is now part of my normal flora.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 05/26/19 11:33 AM

Originally Posted by DadCue
I have no problem with what you are suggesting. I have read similar accounts of antibiotic therapy being used to treat reactive arthritis. I can easily envision an enteric infection causing an acute onset of reactive arthritis. The problem on this forum is that---if you haven't been diagnosed with AS and not taking a biologic, then you are in the wrong forum. It's not that I was treated badly ... I just felt I didn't fit i in. Especially since, I have been taking prednisone for years.

I would have a similar problem convincing my doctor to prescribe Rifaximin since I must have an iron stomach because I never have had any bowel issues except twice. The first time was 25 years ago at the onset of reactive arthritis. The second time, was a presumed case of norovirus and I found myself in an ICU. It sounds like you are suggesting the purpose of Rifaxmin is solely to "seal the gut" and not to treat any sort of infection. I can't help thinking that something has colonized in there that shouldn't have and is now part of my normal flora.


On the contrary, I mentioned that Rifaximin is so good because it is BOTH an antibiotic and an anti-inflammatory agent that also stimulates healing of the gut (and sealing, which is very beneficial to those with HLA-B27 especially.) In the post right above yours, I mention how bacteria get out of balance and Rifaximin brings them into balance. It is of note that it requires only one offense to the gut/immune barrier for the cascade to take place for those with AS. The general progression is intestinal inflammation (from any number of sources, in some HLA-B27,) followed by gut barrier compromise (leaky gut in some, a pathogen in others,) followed by the symptoms of ReA or AS. Another route is the oral pathogen offense, usually periodontal.

To be clear: Rifaximin is an antibiotic so it will DEFINITELY address the infectious element, which is why it is prescribed for Traveler's Diarrhea (an infectious agent,) as well as promote "sealing" of the intestines through tight-junction proteins. It is a double whammy, which is why another woman on another forum experienced profound benefit from it, as well as another member on that forum calling it the perfect fit as a treatment for AS. This was on the kickas forum that I linked above just one post ago.
Posted By: dan321

Re: Potential "Patch" for AS - 05/31/19 11:57 PM

Keep us in the loop of how it's going. Btw I'm surprised there's only one person on Kickas.org who tried Rifaximin! That forum has a long history with many of the members posting about their various experimental treatments.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/01/19 07:06 PM

So, nearly a 2-week update! I barely have any pain whatsoever in my lower lumbar region. I am also sticking now (last 4-5 days) to an NSD to help with the speed of healing; however, I have found that (and theorized myself) happy bacteria can be eradicated more easily. The no starch diet is a good idea to relieve symptoms, but in terms of treating the bacteria that you're trying to eliminate, not feeding them can cause them to go into starvation mode and "sporulate." This means they basically wall themselves off and are much less receptive to antibiotics or antimicrobials in this state, or sometimes they are completely not receptive at all. (LINK) The reason I decided to research this further is that upon eating carbs at all, the pain can come back within a day and ramp up for a few days. To me, this indicates that the cessation is not due to clearance of the offending bacterial strains, but due to the fact that they are less biologically active on the diet.

Today, I am no longer lethargic or "overburdened" by the systemic inflammation response. I can feel when it begins to happen (when I was eating small amounts of carbs) as even my knee, from the surgery, behaves more poorly and aches more, not just my spine. I am 4 weeks post-meniscal-repair and improving much more quickly after having started Rifaximin. I have regularly been taking my heart rate throughout the day as I have a log of this from the past. The results are shocking. My resting heart rate upon waking used to be in the '60s (relatively normal,) however, during the day and/or after meals it was between 75-110, depending on how offensive the meal was to my system or how much stress my body was perceiving/promoting during the day. Consistent heart rate tests now produce results within the 55-62 range, even after meals. I've even done some slightly strenuous activities and my heart rate doesn't move too far and sometimes barely at all. I just feel "calm and relaxed" most of the time.

New approaches towards dealing with what is going on in those with post-infectious IBS/IBD or, like with HLA-B27, an aberrant gut microbiome that can damage the nerve associated with proper gut function, which includes a test that can sense a protein in the blood that almost all people produce when they have these problems. Read the latest update with what's being developed here. There is also a lot of wisdom to be gleaned on the gut/body connection here and how bacteria can be counter-intuitive sometimes. (LINK)

In the vein that feeding the bacteria is more important that starving them FOR TREATMENT, not symptom management, I found these:
(LINK 1)
(LINK 2)
(LINK 3)

These suggest that the theory of using partially hydrolyzed guar gum (PHGG) as a food source to both a) feed and maintain the good bacteria in the gut that you're supplementing through probiotics or diet / or are just residents there naturally, and b) feed the offenders (since PHGG is a carb, it would be metabolized by the bacteria causing symptoms in AS patients.) This gives weight to the argument that feeding bad bacteria and making them happy will make them easier to kill, as the study using Rifaximin alongside supplementing with PHGG showed better outcomes than using Rifaximin alone!

TLDR;
Feelin' good people! Feelin' REAL good!
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/01/19 07:25 PM

Originally Posted by dan321
Keep us in the loop of how it's going. Btw I'm surprised there's only one person on Kickas.org who tried Rifaximin! That forum has a long history with many of the members posting about their various experimental treatments.


They tried Rifaximin under sheer luck because that was prescribed by the doc. However, the other member who claims (in replies later on down the chain) that Rifaximin is "perfect for AS," likely due to the many things I've already mentioned, must have had many others who have had experience with it but never make it to the forums to post (my logical deduction.)

To address why the large groups of people on kickas.org hadn't tried Rifaximin yet either, well that's because the study was just released this year that indicated it's a fantastic drug for this use-case. I doubt many people read as many medical journals as I do per week either. I am CONSTANTLY looking for answers and updating myself, something that many medical docs should do...but do not. I even read an article written about medicine recently where someone literally said the exact same thing, so I at least felt like I wasn't the only one perceiving the medical field this way.

I really hope this post can open peoples' eyes to the possibilities out there that are being developed in understanding how the microbiome really is at the root of a lot of problems, including ones that might seem completely unrelated.
Posted By: dan321

Re: Potential "Patch" for AS - 06/01/19 09:37 PM

Actually it seems there have been a handful of threads about Rifaximin on this forum but you just have to go back several years.

Here a discussion thread on it spawned because of a study about its potential use for treating Crohns, although it seems no one had tried it first-hand:
http://forums.spondylitis.org/ubbthreads.php?ubb=showflat&Number=75506&Searchpage=1&Main=7549&Words=%2Brifaximin&Search=true#Post75506

On this thread one person says "my GI tried it on me about 5 years ago before Humira was approved and I reacted to remicade, I was on a liquid diet at that point, sadly it did not work for me. "
http://forums.spondylitis.org/ubbthreads.php?ubb=showflat&Number=190046&Searchpage=1&Main=17594&Words=%2Brifaximin&Search=true#Post190046
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/02/19 08:20 AM

Originally Posted by dan321
Actually it seems there have been a handful of threads about Rifaximin on this forum but you just have to go back several years.

Here a discussion thread on it spawned because of a study about its potential use for treating Crohns, although it seems no one had tried it first-hand:
http://forums.spondylitis.org/ubbthreads.php?ubb=showflat&Number=75506&Searchpage=1&Main=7549&Words=%2Brifaximin&Search=true#Post75506

On this thread one person says "my GI tried it on me about 5 years ago before Humira was approved and I reacted to remicade, I was on a liquid diet at that point, sadly it did not work for me. "
http://forums.spondylitis.org/ubbthreads.php?ubb=showflat&Number=190046&Searchpage=1&Main=17594&Words=%2Brifaximin&Search=true#Post190046



Yes, that is unfortunate. Given her pain seemed not to respond to ANYTHING, it is likely that there is a confounding variable there. Also, damage done by AS is not reversible, so if her pain is from the mechanical functioning of her joints (which may have been damaged so much that they will always be in pain) then she will not benefit from the Rifaximin treatment. I, however, have had pain for a much shorter duration of time and am seeing improvement, though it's not completely gone. I wonder if I've also permanently damaged some part of my spine and the pain will always be at this low level in certain seated positions? Also, she could have had a confounding periodontal infection from all the stuff she'd tried and that would have never been helped by Rifaximin, or anything else she tried as the invader that was triggering the immunity was not one from the guts. Of course, this is all speculation at this point.
Posted By: dan321

Re: Potential "Patch" for AS - 06/02/19 12:03 PM

Another previously very active forum member, Tacitus, who had strong views on alternative treatments, had tried Rifaximin along with quite a few other antibiotics, and mentions Rifaximin many times, but he doesn't say specifically if it helped him. Anyway I find the concept very interesting.

The note about how it reduced your resting heart rate is also noteworthy, I haven't seen a lot of folks talk about heart rate as a noticeable variable in AS but I will examine my own.

So I wonder what is your plan, to take Rifaximin continually? Once in a while? How would you justify to the doctor to give you a recurring prescription?
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/03/19 06:37 AM

Originally Posted by dan321
Another previously very active forum member, Tacitus, who had strong views on alternative treatments, had tried Rifaximin along with quite a few other antibiotics, and mentions Rifaximin many times, but he doesn't say specifically if it helped him. Anyway I find the concept very interesting.

The note about how it reduced your resting heart rate is also noteworthy, I haven't seen a lot of folks talk about heart rate as a noticeable variable in AS but I will examine my own.

So I wonder what is your plan, to take Rifaximin continually? Once in a while? How would you justify to the doctor to give you a recurring prescription?


Generally, I find that attacks to my body raise my heart rate. The inflamed lining of my intestines causes a lot of foods to be triggering to my system. I'll notice sweating, lethargy, fatigue, etc. I have kept a log in the past, and my resting heart rate was 62ish upon waking from sleep. Doing any kind of normal activity and then sitting down, if not under attack, would be around 72+. If my body was under stress from the food I ate, it would be around 88-115, with 115 being a food that really irritated me. Granted, I am now eating a very very low starch diet...I now check my heart rate and notice that I am around at a much lower 55 bpm. Some days it will spike up to 88-90 when I am having a weird attack or something is "flaring." I am currently flaring SIGNIFICANTLY less and with less magnitude than before. Still continuing with Rifaximin, will keep you all updated!

Also, I mentioned in my first post you cannot take it indefinitely, you must take it in cycles...or it can upregulate your absorption of triglycerides and cause fatty liver. As for how to get more, currently working on it. I have some unorthodox options but am trying to go the "legit" route. This would involve showing docs the increasing amount of evidence that's piling up in dozens of studies that shows its effectiveness in treating IBS, not just SIBO and IBS-D.
Posted By: The_Inflammator

Re: Potential "Patch" for AS - 06/04/19 03:33 PM

Looks like this could be a powerful tool to be able to use it as needed long term for AS.Minimal side effects, killing the bad bacteria and correcting leaky gut. Looks like it is pretty expensive if insurance isn't cover it though. The trick would be figuring out how to get insurance to cover a long term continuous supply. I guess it would only ever be prescribed on a short term basis even for those of us with obvious IBD. Maybe that will change in the years to come. I'd love to be able to try it but would hate if i was told i had to stop while it is working.
Posted By: dan321

Re: Potential "Patch" for AS - 06/04/19 04:26 PM

I am going to ask my family doctor to give me a prescription for Rifaximin. For my AS, he strongly warns me not to take NSAIDs due to my UC and use of blood thinners, telling me he's seen too many disaster scenarios in the ER where long-time NSAID users die from internal bleeding and that I would be at high risk. He also recommends not taking biologics due to the various risks and problems associated. So when I ask him "so, what should I do?" he just says "sounds like you're between a rock and a hard place". Not very helpful! I still take celebrex periodically but am very scared about it and try to do so sparingly, but lately it's just been unliveable unless I take it every day.

So, I will show him the study from March on Rifaximin curing AS in mice, and the other study from 9 years ago about Rifaximin having positive effects on people with Crohns, and see what he thinks. I suppose the other way to do it would be to pretend I have traveller's diarrhea but just don't think I could be dishonest with the doctor no matter how unhelpful he's been thus far.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/04/19 05:54 PM

Originally Posted by The_Inflammator
Looks like this could be a powerful tool to be able to use it as needed long term for AS.Minimal side effects, killing the bad bacteria and correcting leaky gut. Looks like it is pretty expensive if insurance isn't cover it though. The trick would be figuring out how to get insurance to cover a long term continuous supply. I guess it would only ever be prescribed on a short term basis even for those of us with obvious IBD. Maybe that will change in the years to come. I'd love to be able to try it but would hate if i was told i had to stop while it is working.


Originally Posted by dan321
I am going to ask my family doctor to give me a prescription for Rifaximin. For my AS, he strongly warns me not to take NSAIDs due to my UC and use of blood thinners, telling me he's seen too many disaster scenarios in the ER where long-time NSAID users die from internal bleeding and that I would be at high risk. He also recommends not taking biologics due to the various risks and problems associated. So when I ask him "so, what should I do?" he just says "sounds like you're between a rock and a hard place". Not very helpful! I still take celebrex periodically but am very scared about it and try to do so sparingly, but lately it's just been unliveable unless I take it every day.

So, I will show him the study from March on Rifaximin curing AS in mice, and the other study from 9 years ago about Rifaximin having positive effects on people with Crohns, and see what he thinks. I suppose the other way to do it would be to pretend I have traveller's diarrhea but just don't think I could be dishonest with the doctor no matter how unhelpful he's been thus far.


Yes, I completely agree. I felt the same way and presented the studies; however, it never played out in my favor. It seems like doctors get really upset when it seems like you are acting like you "know more than they do." However, we are just constantly on the lookout for something better and a way out, whereas most of the time they don't keep up regularly...but they obviously should. They could look at me in severe pain and tell me things that would require me to wait for over a month longer (damage is irreversible in AS) all because they weren't convinced that the insane amount of evidence I've gathered was enough to justify certain courses of action. Hypocratic oath seems much more like the hypocritical oath to me in today's medicine. There are those of us that are intelligent enough to find answers for ourselves out there, and could even have something to offer medicine. I was educated in science...I understand when inferences can be made and when they cannot. I understand that it requires repeated trials of a theory that show reproducible results in order to draw conclusions. I've done all of that in my own research on multiple different studies showing the same findings, etc. It doesn't seem to matter to them.

I also want to be clear, just so your expectations are not improperly set: Rifaximin does not cure AS in HLA-B27+ people...it is only a patch. In those who follow a strict diet and keep gut inflammation low, it may happen to stave off the disease for quite a long time thereafter. However, HLA-B27 automatically predisposes people to gut inflammation and, eventually, the issues return due to this, as bacteria are affected by the state of the gut. If you are NOT HLA-B27+ then perhaps Rifaximin can be a potential cure if you don't continue to behave in a manner that put you towards the disease, to begin with. If this was you traveling and then catching something or some other such one-off event...then I don't forsee relapse.

Since Rifaximin is now being used in the treatment of IBS, not just Traveler's Diarrhea (or IBS-D,) I think that is an avenue that could play out long-term. The first run is 2 weeks. Then you can get your doc to approve another 2 weeks, which is accepted by Salix if the first two weeks aren't enough, which you should easily be able to just tell a doc you don't feel you've had complete remission of symptoms. Once that is done, you should see some significant improvements.

To MAINTAIN I would highly recommend that all those with issues that stem from HLA-B27 consider incorporating "bone broth" into their diets to help repair the guts and keep a strong barrier. Kettle and Fire arguably make some of the best bone broth products you can order on the internet and I am considering a monthly subscription model. (Kettle and Fire) Maintaining a healthy diet as well, which I have mainly been on the low-starch/no-starch diet and maintaining ketosis. This has been very helpful for me in many ways, not all of which are related to the management of AS symptoms. Most notably my energy is longer-lasting and my hunger is more of a low-grade constant thing, instead of ever getting "hangry" or shaky, etc. My thought processes are clearer and I require less "activation energy" to get things started. Don't forget the study I showed recently, that taking partially hydrolyzed guar gum (PHGG) alongside taking Rifaximin worked significantly better than taking Rifaximin alone. The supplement is cheap and can be found on GoodGutSolution (an IBS/IBD related site) at a discount, or on Amazon too. (Good Gut Solution) (Amazon). The rate of "relapse" was much lower when using PHGG, thus concern of not getting future rounds of Rifaximin would be reduced (if you are not HLA-B27+.) If you decide to use PHGG, remember to start SUPER slow. Don't just start taking the recommended 2 scoops a day with meals and with your medication (in this case Rifaximin.) I spoke directly to the company and they recommended starting from 1/4 tsp or tbsp and working your way up. This was based on my theory, and the links I showed to support it, that keeping bacteria fed helps you kill them faster than starving them.

For those of us that are HLA-B27+, the bone broth is essential to keeping a barrier between the gut and the microbiome in place so that leaking doesn't occur. Other things to consider are taking butyrate, which promotes epithelial cell integrity (I believe I mentioned this in another post.) It's because of an improper firmicutes to bateroidetes ratio that butyrate production is skewed in HLA-B27 and gut integrity eventually gets compromised. So, helping to shift this back with butyrate supplementation for the long-term might also be a really helpful tool. I shared the links regarding the imbalance and the production of acetate vs butyrate in each of those categories of bacteria in another post before. Here is one of the best companies on the market for a quality butyrate supplement. (Butyrate)

Please remember that before taking these courses of action you MUST determine whether your AS comes from:

1) HLA-B27 related intestinal inflammation and dysbiosis (they go hand-in-hand.)
2) An offense of the gut not related to HLA-B27
3) An offense elsewhere, like periodontal infections

Rifaximin can only really be of help in cases 1 & 2. If you have some periodontal issues, Rifaximin only acts within the gut and you will still be in pain and reap very little benefit. However, Rifampicin is systemic (which means side effects will also be much worse!) I have recently read about those who suffer from Reactive Arthritis (ReA.) A study was done that showed that Rifampicin combined with doxycycline or azithromycin worked quite well to completely halt the syndrome/disease in affected peripheral and axial joints, perhaps even acting as THE CURE. One could not really tell unless tissue was further biopsied after the individual claimed that no symptoms were detected at the 9-month post-study mark, which was these biopsies were not done; the patients merely attested to remaining symptom-free. This is because ReA IS (no question anymore because various articular fluid and cartilage samples have shown bacterial cells in the affected joints) a disease related to having an "infection" in your joints where the bacteria no longer replicate, but change their DNA and cellular structure to hijack your own synovial fluid cells to make their proteins for them, usually indefinitely. The reason they cannot be cleared is that, usually, people who have an issue produce lower IFN-gamma in their cartilage, as is a common issue in those with HLA-B27. So, we have yet another match-up for symptoms in the bacterial model. I might try this combination antibiotic therapy in the near future as I also have ReA that is NOT affected by Rifaximin. Check the study out if you are interested. (LINK)

So, for those of you that suffer from other syndromes in the SpA category, such as ReA/scleritis/iritis/uveitis...this may be a good avenue to look down (the combination therapy above.) Generally, uveitis/scleritis is your body reacting to various proteins and other compounds created by specific bacteria. It would make sense that someone with ReA would also start having issues in the eye. Also, sometimes it requires that you go on to develop AS with ReA first before the eye complications show up. This is likely related to the way TLR's work (Toll-Like Receptors.) They only act a certain way once certain conditions have been met, or are continually present. I don't have the study quickly on hand to demonstrate this effect, but it makes COMPLETE sense from what I've read.

Let's keep going and get people free of this dang set of syndromes baby!
Posted By: dan321

Re: Potential "Patch" for AS - 06/05/19 01:43 PM

The Rifaximin sounds interesting because there's a study out (can't imagine 1 study is conclusive but at least it's a start). But once you get into NSD, bone broth, gut dysbiosis, etc. it does start to sound like pseudoscience... I followed NSD religiously for 6 months on the suggestion of many in the Kickas forum but it didn't do anything for me except make me lose tons of weight, look and feel awful, and drive my family crazy with all the food restrictions and iodine-testing, etc.. In fact I felt great when I finally started eating normal food again.

Bone broth is an expensive fad, no? I didn't see the mice in the Rifaximin study having to drink bone broth smile smile

Obviously there must be something to these things or there wouldn't be so many fervent supporters out there but I found the evidence for it to be weak, and obviously what I actually cared about - results - just weren't there for me.
Posted By: The_Inflammator

Re: Potential "Patch" for AS - 06/05/19 06:13 PM

Sounds kind of like my experience with NSD. It worked very well for me on my AS and IBD by itself but it suuuucked. Never been so pain free and miserable. Felt like my brain was on auto-pilot.I was just done after a few months. If an antibiotic worked well only in conjunction with lifelong NSD, I would just resort to NSD again.

Bone broth doesn't have to be expensive if you make it yourself. I don't have hours of daily access to a kitchen to make NSD work though.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/05/19 06:54 PM

Originally Posted by dan321
The Rifaximin sounds interesting because there's a study out (can't imagine 1 study is conclusive but at least it's a start). But once you get into NSD, bone broth, gut dysbiosis, etc. it does start to sound like pseudoscience... I followed NSD religiously for 6 months on the suggestion of many in the Kickas forum but it didn't do anything for me except make me lose tons of weight, look and feel awful, and drive my family crazy with all the food restrictions and iodine-testing, etc.. In fact I felt great when I finally started eating normal food again.

Bone broth is an expensive fad, no? I didn't see the mice in the Rifaximin study having to drink bone broth smile smile

Obviously there must be something to these things or there wouldn't be so many fervent supporters out there but I found the evidence for it to be weak, and obviously what I actually cared about - results - just weren't there for me.


Originally Posted by dan321
Sounds kind of like my experience with NSD. It worked very well for me on my AS and IBD by itself but it suuuucked. Never been so pain free and miserable. Felt like my brain was on auto-pilot.I was just done after a few months. If an antibiotic worked well only in conjunction with lifelong NSD, I would just resort to NSD again.

Bone broth doesn't have to be expensive if you make it yourself. I don't have hours of daily access to a kitchen to make NSD work though.


I was very careful in choosing my words, and have provided TONS of studies for every claim I've made. I don't think I am the type to be touting pseudoscience...I just try things, research them, and see if they work. Bone broth is not pseudoscience by any stretch. The intestines are made from collagen and AS is a disease of the body destroying collagen. Bone broth happens to be easy to digest and is a source of collagen. It isn't a "fake supplement" with other fillers in the pill capsules, etc. The bone broth I mentioned is also of the highest quality and cooked with veggies, so as to contain a lot of nutrition. I had a VERY hard time digesting vegetables for a while and this would be a good way to gain both collagen proteins (yes you can get them elsewhere) and minerals from an easy to digest drink. I am not purporting you couldn't do the SAME elsewhere. If you'd like to source collagen and other minerals elsewhere, be my guest.

Yes, it is slightly expensive, but I have wholeheartedly seen that you get out what you put in, in terms of my health. If you don't have time to make bone broth yourself, join their subscription plan and have 1 or 2 of these drinks a day for a while and see how you feel. I am not the type of person to knock something before I try it if it doesn't seem there is any harm in it. I even took Rifaximin to SEE what would happen, which is a drug and has the potential to harm me. I then shared the results with everyone else so that they could share in potential healing benefits. This is science, and this is my body I am trying to save...if I am unwilling to drink bone broth and see how much it helps...how much do I really want to get better?

To comment on "the mice in the study didn't need to have bone broth." No, they didn't. However, their inflammation markers only returned 60-75% back into a "more normal" range. Imagine the benefits of assisting the reduction in inflammation of the intestines even further with intelligent dietary choices, because that's clearly what this disease is about. Not everything needs to have a scientific study to prove it. Some things are, indeed, just common sense. Eating too much candy (a dessert and not a meal) will be bad for you over time. People have said this for at least a hundred years with NO scientific studies. Turns out to be true. Similarly, eating an easily digestible source of protein/collagen/gelatin that the body needs is obviously going to confer benefits. Not many studies have been done, and most of them aim to attack "inconsistent amino acid profiles" or "high heavy metal contents," however neither of these really matter. 1) Consistency in the amino acid profile isn't really necessary, in order for healing to occur, because digestive processes vary in efficiency anyway (and are around 20% efficient at best.) The idea is to provide a soothing source of these compounds that don't require a pill coating, etc. 2) The amount of the elevated levels of heavy metals is still WELL WITHIN the daily safety limits of the metals they were testing for, so this is merely scare-tactics. It turns out all meats, seafood, etc. have higher levels of heavy metals in them (like lead.) This is just the nature of accumulation in organic beings.
Posted By: The_Inflammator

Re: Potential "Patch" for AS - 06/06/19 11:11 AM

I'm not knocking what you are doing at all. I definitely believe Antibiotics and NSD eliminate AS inflammation. NSD brought AS pain to 0 and restored full flexibility in about 3 weeks. Never tried antibiotics but i believe I would have had even faster results. Would be nicer if an Antibiotic just did that job on their own while keeping a normal diet. My brain didn't do well without the carbs and nutrients so I stopped at 4 months. I turned into Bran in the last 2 seasons of Game of Thrones. A cold empty vessel. I didn't even get any cool warg abilities. It was not pleasant.

A lot of people take 2 sides on the NSD debate. I am sort of in the middle. I know it works but it reduces my quality of life and impacts my mind. I know it is all relative and someone with Severe AS would accept my side effects as minor annoyances for the pain relief I had. I think we can do better in the future. I hope. I am trying new things now.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/06/19 08:06 PM

Originally Posted by The_Inflammator
I'm not knocking what you are doing at all. I definitely believe Antibiotics and NSD eliminate AS inflammation. NSD brought AS pain to 0 and restored full flexibility in about 3 weeks. Never tried antibiotics but i believe I would have had even faster results. Would be nicer if an Antibiotic just did that job on their own while keeping a normal diet. My brain didn't do well without the carbs and nutrients so I stopped at 4 months. I turned into Bran in the last 2 seasons of Game of Thrones. A cold empty vessel. I didn't even get any cool warg abilities. It was not pleasant.

A lot of people take 2 sides on the NSD debate. I am sort of in the middle. I know it works but it reduces my quality of life and impacts my mind. I know it is all relative and someone with Severe AS would accept my side effects as minor annoyances for the pain relief I had. I think we can do better in the future. I hope. I am trying new things now.


I hear you man. I have been trying to make it clear (the following facts):

1) Simply changing your diet will reduce the symptoms but not the cause (you starved the bad bacteria your body fights, they go into hibernation.)
2) Simply taking the antibiotics without slowing down the offensive material you have in your diet will take a long time, but is POSSIBLE. Just hard to get Rifaximin prescription that long...

Because of 1 & 2, one should feed the gut "minimal" starch, but still some, like from Partially Hydrolyzed Guar Gum and maybe a few carbs like 10 corn tortilla chips, or a few bites of rice, per day. Feeding the bad bacteria just enough to stay alive, but not enough to thrive will keep them from entering hibernation and "walling off" their cell walls via a starvation response. Then the antibiotic (Rifaximin in my case) can exhibit its effects and reduce the population of that bacteria.

I suggest both because it is the optimal path to recovery. You will never actually be truly better following only dietary changes because you are harboring hibernating bacteria. Once your NSD + Rifaximin (or potentially metronidazole as mentioned in some other studies I posted earlier) course is complete, see if you've eliminated the bacteria by eating small amounts of carbs without the treatment. This is the angle I am playing, and it seems to make sense to me from all the different avenues of research I am bringing together.

Note:
Of course, all of this is irrelevant if your AS source is the mouth. Rifaximin won't work on infections other than what's going on in the gut, so getting your oral bacteria cultured or having your immunoglobulins tested to see what your body is "fighting" is the smartest first step in identifying which vector your AS is spawning from. Since I am HLA-B27+, I started with the gut because that gene predisposes me to gut issues and I have had them my entire life, basically.

I believe Rifampicin will work well for those with infections elsewhere, as well as those with Reactive Arthritis (which I will be trying to tackle next.)
Posted By: PainintheAS

Re: Potential "Patch" for AS - 06/10/19 08:30 AM

Dug up one of the studies I had in my research list that explains, in more detail, exactly the effects that Rifaximin has on the gastrointestinal tract. I will paste the excerpt because I think it is of notable mention:

Although its poor gastrointestinal (GI) absorbability leads to low systemic blood levels, fecal concentrations remain elevated with unchanged drug[3,7]. Rifaximin does not cause drug-drug interaction and does not alter intestinal or hepatic cytochrome P3A activity[8].

Rifaximin has in vitro antimicrobial activity against Gram-positive and Gram-negative, aerobic and anaerobic flora[9]. The increased solubility of rifaximin in bile (an estimated 70- to 120-fold increase in solubility in vitro compared to aqueous solution)[3] leads to higher luminal concentrations and enhanced antimicrobial effects[10] against enteric bacteria, with possibly larger effects in the small intestine compared with the more aqueous colon[3] as well as low microbial resistance[11] with minimal effect on colonic microflora. In addition to its direct bactericidal effect, rifaximin has been shown to reduce bacterial virulence factors and morphology[12], the inflammatory response expected from virulent strains of enteroaggregative Escherichia coli (E. coli) (EAEC) and Shigella, bacterial epithelial attachment and plasmid transfer from donor to recipient strains by > 99% for bacteria resistant or susceptible to rifaximin[12], and to provide cytoprotection through altering cytokine expression and mucosal inflammation by activation of pregnane X receptor involved in detoxification and elimination of foreign chemicals and toxins in the gut in disease states[12,13].


For IBD, I mentioned at the meetup today that people with HLA-B27 have impaired mucosal functioning in the gut. I mentioned one strain that I completely butchered the name of, nevertheless, it is also mentioned in the study as having its growth promoted by Rifaximin (note metronidazole is also mentioned here, which is the other antibiotic that has been used IN HUMANS to help with AS with great success, in trials, that I posted in my first article. These drugs are helping IBD, but yet also help with AS. I will continue to stand behind the strong evidence that shows treating IBD and the associated leakages/failures of the intestinal tract will be essential in effectively treating AS. There are just so many cross-confirming statistics in my opinion):

The pathogenesis of inflammatory bowel disease (IBD) remains poorly understood. It is hypothesized that the gut microflora plays a role in the initiation and/or perpetuation of the process[140,141]. Antibiotics have a well-established role in the treatment of septic complications of IBD. Their benefit in the primary treatment of IBD is not well elucidated, however they are still commonly used in practice. Several trials have been carried out with metronidazole, ciprofloxacin, clofazimine, and other combinations. They appear to be useful in the treatment of Crohn’s disease (CD)[142-144], ulcerative colitis (UC)[145] and pouchitis; however, prolonged use of these antibiotics is associated with various systemic side effects. Based on observational data, rifaximin was associated with some improvement in IBD. Rifaximin reduces development and to promote healing of colitis in mice by reducing bacterial translocation[146]. Rifaximin may improve the existing dysbiosis in patients with CD by modulating colonic microbiota and increasing Bifidobacteria and Faecalbacterium prausnitzii147]. Rifaximin may also exert anti-inflammatory activities by increasing expression of pregnane-X-receptor and antagonizing the effects of tumor necrosis factor-alpha (TNF-α) on epithelial cells in vitro[148,149].

Faecalbacterium prausnitzii was the one I mentioned at the meetup. It is mucin-degrading, which means it thrives on the gut lining. In the right amounts, this particular bacteria can stimulate the production of more mucin by the body and help keep a healthy barrier. It also produces butyrate, which is a cellular energy source for colonic cells (I mentioned this in a prior post.) Basically, Rifaximin can help keep the stimulators of your mucosal production nearby, and in turn, they feed the colonic cells more butyrate to help promote a tight gut lining with low permeability.

The study goes on to mention that Rifaximin, due to it's anti-inflammatory effects, proved beneficial in Crohn's Disease (CD,) Ulcerative Colitis (UC,) and few other intestinal ailments. To address the statements earlier that using antibiotics can be associated with changes in the microbiota and that it is unknown whether these changes are good or bad...I would like to provide some information from the study that demonstrates the extreme safety of Rifaximin even at high dosages:

The effect of intermittent high-dose rifaximin (1800 mg daily in 3 treatment periods of 10 d, each followed by 25 d of washout) on enteric bacteria (enterococci, coliforms, lactobacilli, bifidobacteria, Bacteroides spp., and Clostridium perfringens) was studied in patients with ulcerative colitis[178]. After each washout period, concentrations of the bacteria tested returned to initial values, suggesting that the administration of high doses of rifaximin does not significantly modify the colonic microflora. Rifaximin-resistant isolates were found, mostly in Bifidobacteria and have documented rapid disappearance of bacteria resistant to rifaximin from the intestinal tract upon treatment washout[179].

Real life data are also available from studies on susceptibility alterations of bacterial isolates causing TD from different geographic locations and over time[180,181]. Bacterial isolates from individuals with TD while visiting India, Mexico, Jamaica or Kenya in 1997 were challenged against different antimicrobial agents, of which rifaximin demonstrated an intermediate activity with MIC50 of 16 μg/mL and MIC90 of 32 mg/L[180]. Around 10 years later, reevaluation of susceptibility changes in Mexico, India and Guatemala between 2006 and 2008 demonstrated no change in the MIC of isolates to rifaximin while other antimicrobial agents (e.g., fluoroquinolones, cephalosporins, azithromycin) had a significant increase in their MIC levels compared to bacterial isolates from a decade earlier[181].

Based on the above, rifaximin use appears to be associated with a low incidence of development or persistence of spontaneous bacterial mutants. Moreover, the development of important drug resistance among extra-intestinal flora during rifaximin therapy is unlikely because of minimal systemic absorption and limited cross-resistance of rifaximin with other antimicrobials.


This is why Rifaximin is such a great choice. It has minimal effect on the microbiome in comparison to other antibiotics, is not well-absorbed by the body (so it won't cause bacterial imbalance elsewhere,) has anti-inflammatory effects, stimulates pathways that help with cellular detoxification, does not form drug interactions, rarely causes any resistance to develop (and even when it does...the effect is cleared from these resistant bacteria which end up returning to normal,) and has cytokine and TNF-α regulating capabilities (which DIRECTLY demonstrates that it will have an effect on AS by specifically regulating two of the inflammatory markers that current drugs are aimed at targeting.)

All of this, plus the testimony from others on kickas.org as well as myself add up to be convincing for the case of using Rifaximin to treat AS right down to the fundamental imbalance in the system, bypassing the need to blunt entire arms of your immune system with biologics. Rifaximin will affect the same targets, but by regulating their production and not interfering with their communication to the body (which is necessary for proper immune function.) Really hoping people can convince doctors to let them give this a try.

Link to Study
Posted By: The_Inflammator

Re: Potential "Patch" for AS - 06/10/19 09:42 PM

Well keep up the treatment if you can. The study you linked to in your first post about the fatty liver issue seemed to indicate it would take a lot longer than 3 months to become an issue in humans with the mice/human life span ratio of 1:50.
Posted By: FayeK

Re: Potential "Patch" for AS - 06/15/19 03:02 PM

Bless you all that have the time, intelligence and energy to read all these scientific papers. My old brain doesn't understand most of what you said but I feel I got the just of it. Hearing your thoughts are very helpful to me. I have nothing of substance to add to the discussion. I only post to let you know, I appreciate very much what you are sharing. Thank you.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/11/19 09:20 AM

Hey all!

Some more interesting developments as I scour the net for papers. One thing to note, I just had my periodontal bacteria tested, and I did come back with some pathogens that MIGHT be contributing to my disease state some. I am going to be treating them and see how I feel over time. However, here are my interesting finds:

1) I have found yet ANOTHER mention of the "great effectiveness" of Rifaximin (actually another derivative Rifamycin). This paper lists the many periodontal pathogens that can affect the gums, as well as the subset that can be linked with AS (which was also in the articles on the first post I submitted.) Other drugs listed as significantly effective in treating AS: Moxifloxacin & Sulfazine (The latter being more effective in peripheral pain than axial pain.) It is also interesting to note that those with pain in the joints could benefit from "intrasynovial rifampicin" administration (Rifampicin is yet ANOTHER derivative in the Rifaximin group.) Way to go for the Rifa family of antibiotics! (Warning: Rifampicin is unlike Rifaximin or Rifamycin in that it IS absorbed by the body, whereas the others are not. So side effects will undoubtedly be much more obvious when using Rifampicin.

Link

2) This has to be one of the most amazing theories to explain all that is going on with AS. Basically, AS attacks the joints/tendons where tensile stress is the highest. Normally, these areas cannot be attacked by the body because specific compounds are released in order to keep the processes of inflammation and digestion away from areas that are constantly under load. It turns out that in HLA-B27+ individuals, this tensile stress response is not enough to keep the body from attacking these locations due to some very interesting mechanics of the HLA-B27 structure and chemical binding. I purport that there are likely many other such similar oddities in other individuals that are not HLA-B27+ that will, when stressed, influence an arthritogenic cascade of inflammatory chemokines. To support this fact, I have always had pain, even as a young child, in my tendons when doing things others can do with ease. For example, resting my foot (heel) on the coffee table while sitting at the couch. A few minutes later (after the underside of the leg has been slightly hyperextended) when I lift my leg off of the table, it is VERY painful for a few seconds. The same thing has been true when I used to work on my computer, where you have to lean over to look at the internals. After a few minutes, my lower back would be achy as hell...and then I stand up and it's gone. Super interesting!

Link

Just want it to be clear that MANY avenues of research, anecdotal evidence of people on other forums I've shared here, as well as myself have had GREAT success with treating this in a more holistic manner. Addressing the guts in order to balance/regulate cytokine production and interleukins rather than blocking them completely. I continue to stand by this as the best treatment, though it might not be the fastest acting or most pain-relieving. I feel as if your pain goes from a 7-10 down to a 1-3, without severely hindering your immune system...then this is the path to go down. Further improvements in this path/treatment will come. You cannot really...come back from jacking with your chemokine pathways using auto-antibody drugs. They don't even want people entering clinical trials who have used biologics before...and there is likely a reason for that.

I hope you are all doing well!
Posted By: Braxon

Re: Potential "Patch" for AS - 08/12/19 11:20 PM

While I am partial to things with a containing a letter X, my personal inclination is always- oh a drug, so we can enable someone to have temporary alleviation or partial healing, but without an individual learning new health practices (better diet, better oral hygiene). Aka just take this pill and no worries.
Seems like cheating (them) slightly. No?
I would agree that it may be very helpful in a very bad patient who has problems digesting, maybe as a transition to healthy flora along with fermented foods and drinks.
Many times a complete diet overhaul is necessary for actual permanent healing and adaptation. I did a 21 day live food juice blend along with ceasing alcohol and soda, stacked with dried Astragalus and Turmeric roots,, about 6 years ago, and rarely have had any IB since.

Side note: Ever wonder why so many Central and South American people [and India] in countries with poor water supplies stay healthy? Are "Westerners" just weak in the gut? Mayybe it has something to do with the fact that many of us think tabasco sauce is "HOT". Anybody know the full antibacterial and antiparasitic effects of real red hot chilli peppers? 🌶🌶🌶🌶🌶🌶🌶🌶🌶

But that study indicating periodontal makes a ton of logical sense. In fact my belief is bacteria are drivers behind many many many disease, both physical and mental. We each are planets of bacteria really. Certain resistant Staphylococcus can hide out in joints and worsen an already bad condition.

But beyond my realism, my metaphysical friend wants you all to know she purports arthritis is a disease of indecision and lack of yin/yang agreement.
Something something Quartz crystal 😁
Posted By: PsSpa_M_1989

Re: Potential "Patch" for AS - 08/15/19 03:44 AM

PainintheAS:

First of all, thank you for posting a very thorough topic discussion. Your self-conducted research is very valuable to others here. Because I live with someone who is a PhD in Biological Engineering and worked as a researcher and manager for a couple of Top 10 pharma companies, I know a few things from the other end of the aisle. Allow me to offer the following thoughts:

- There are plenty of research studies that noted promising outcomes in animals (usually: mice), only to turn out not to be effective in humans. Actually, even when a drug shows promise in humans with a real study, most will fail when it is put under more scrutiny. This is one of the reasons that pharma companies charge us outrageous prescription prices: They need to finance all failed drugs in the hunt of that one magic combination that will work. I'd just like to offer this view since you are choosing not to go on the available state-of-the-art treatment in the pursuit of a more experimental treatment.

- Considering the complexity and symbiosis of bacteria in our gut, in curiosity how do you determine:
a) This type of drug kills off the bacteria that do more harm than good?
b) The same bacteria won't return?
c) If yes to a) and b), the removal of bacteria will not cause other problems?
d) Are other bacteria or gut mechanisms involved in propelling spondylitis, if so, are those eliminated to?

- How are you benchmarking and following up your condition? Biomarkers? X-rays? Which efficacy does your experimental treatment show?

To me it seems that you are trying to fix the disease at the most upstream condition in the body, although not thoroughly researched or known. As you noted, the alternative is to turn off the problem downstream, with other possible side effects.

Since you started the treatment, which improvements have you noticed?

Thanks,
PsSpa_M_1989
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/16/19 09:42 PM

Originally Posted by Braxon
While I am partial to things with a containing a letter X, my personal inclination is always- oh a drug, so we can enable someone to have temporary alleviation or partial healing, but without an individual learning new health practices (better diet, better oral hygiene). Aka just take this pill and no worries.
Seems like cheating (them) slightly. No?
I would agree that it may be very helpful in a very bad patient who has problems digesting, maybe as a transition to healthy flora along with fermented foods and drinks.
Many times a complete diet overhaul is necessary for actual permanent healing and adaptation. I did a 21 day live food juice blend along with ceasing alcohol and soda, stacked with dried Astragalus and Turmeric roots,, about 6 years ago, and rarely have had any IB since.

Side note: Ever wonder why so many Central and South American people [and India] in countries with poor water supplies stay healthy? Are "Westerners" just weak in the gut? Mayybe it has something to do with the fact that many of us think tabasco sauce is "HOT". Anybody know the full antibacterial and antiparasitic effects of real red hot chilli peppers? 🌶🌶🌶🌶🌶🌶🌶🌶🌶

But that study indicating periodontal makes a ton of logical sense. In fact my belief is bacteria are drivers behind many many many disease, both physical and mental. We each are planets of bacteria really. Certain resistant Staphylococcus can hide out in joints and worsen an already bad condition.

But beyond my realism, my metaphysical friend wants you all to know she purports arthritis is a disease of indecision and lack of yin/yang agreement.
Something something Quartz crystal 😁


Why are westerners weak in the gut? This is a LOADED question.

1)
Yes, the diet has much to do with it. However, diet was never going to fix my issues. HLA-B27 predisposes individuals to either subclinical or clinical levels of inflammation indefinitely, as it HLA molecules affect antigen presentation and inflammation responses. My diet has changed MANY times. I've tried juice cleanses, no carbs / low carbs (works the best so far), vegan, etc. I now cook all my meals at home. Very low carb, lean meats (like turkey), fish, etc. Throughout every diet, there still exists pain, inflammation, and digestive issues. They are transient. Exist for one week, gone for 2 days, then back again, etc. I eat healthier than ANYONE I know, yet I suffer more problems than anyone I know. I've taking turmeric, curcumin, krill oil, astaxanthin, etc. Before my infection in Mexico, these things had some positive effect, albeit only 10-15% alleviation of joint pain, etc. After the infection, my immune system is on constant alert. This is so much more than diet for people with HLA-B27. Let's not forget...how many copies of HLA-B27 and how many other genes that act in conjunction with processes affected by HLA-B27 that individuals might have variants in also affect how this disease presents itself. I also have tried fermented foods a number of times and have been HARMED by them many times. Right now I am making my own L. reuteri yogurt with a lot of success. Many articles on the benefits of two specific strains of L. reuteri. I can attest that they do "calm" things down a bit.

2)
Westerners (of European descent) have the highest prevalence of the HLA-B27 gene, compared to other ethnic groups. This rate is particularly high in Jewish ethnic groups because of the selective breeding that occurred in the Ashkenazi group (they were considered the most intelligent people hundreds of years ago, having their hands in business and finance.) They wanted to increase intelligence so they only mated with other Ashkenazi Jews. This did have the intended effect, but it also thinned genetic diversity, allowing for the expression of many recessive genetic disorders to surface in their population. My family happens to be half Ashkenazi.

3)
Westerners are not brought up in "dirty" environments. Being too clean can affect immunity by not allowing for a diverse intestinal flora, which is described as being the hallmark of optimal health. People in India live in highly polluted areas, with parasites and other bacteria in the water. Sure, their diet can be attributed to some of their health. However, we now know that people who grow up in germ-free environments don't develop proper immune system responses. It is the introduction of foreign bacteria that stimulate and help shape the immune response, by upregulating gene expression of various T-Cells, etc. Also, parasites have a calming effect on the immune system...which is necessary for their survival. They downregulate the immune response in order to stay alive within the host. This is actually an approach taken for many autoimmune disorders (though radical, it is gaining popularity.) People have swallowed pig parasite eggs, etc. They don't survive in the human body long enough but still express their downregulating effect.

4)
Regardless of diet including or not including the herbs and spices of other cultures, the western diet contains more fillers, emulsifiers, and preservatives than other cultures. Other governments and regulating bodies have banned specific substances that we use regularly. These are indigestible, and thus get stored in fat cells and can react with other things later in life.

5)
Rampant overuse of antibiotics by doctors in America has created super-resistant strains of bacteria, reduced overall microbial diversity, and damaged the gut linings of pretty much everyone in America. Couple this with the overuse of NSAIDs and pain-relieving medications, which are EXTREMELY damaging to the gut and you have a pretty clear picture of why American's guts are "more sensitive" than other places in the world. It's not simply our diet alone. If you look up the deaths related to NSAIDs, it is shocking. People bleed to death from ulcers.

-----

To answer your question about "simply taking a pill" being "cheating." I have hated medicine for a long time. I've taken the natural approach to everything. Once again, none of those things were going to work when my genetics predispose me to these issues and an altered response to bacteria. I am unaware of anything in nature that upregulates tight junction protein synthesis in the gut. To be clear, Rifaximin is made from BACTERIA. It is a product of a certain bacteria, because bacteria create products that kill other bacteria in order to stay competitive in their environments. It just so happens that this particular product also has anti-inflammatory effects and tight-junction protein upregulating effects. Do I consider this cheating? No, I desperately needed this because NOTHING else was working. When your body upregulates inflammation, it upregulates TNF-alpha, which INCREASES intestinal permeability. Eventually, you are going to reach a critical failure in the intestinal lining, and that's when true disease symptoms begin to show. I went the western medicine route because Rifaximin (and all Rifa-derivatives are absolutely amazing in that they have the targeted and intended effect with little-to-no side-effects.)

Chili peppers are delicious and I love spicy food, however, I have very little intestinal mucosal lining left. Chili peppers will further irritate the intestines because there is no mucous membrane left in order to buffer the spice from coming in direct contact with the lining of my intestines. Capsaicin, the compound responsible for the level of spice in peppers, is actually an irritant. It UPREGULATES inflammation in order to cause a healing response. However, in people with AS and other inflammatory diseases, there is already an INCREASED inflammatory response and further upregulating that is only going to cause more issues. Too much spice is also known to cause ulcers, so this is just a bad idea for those with gut issues already. Your approach (diet) is a one-size-fits-all approach. It simply doesn't work that way. Some of us are, indeed, different. What's good for one person is NOT good for all.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/16/19 10:23 PM

Originally Posted by PsSpa_M_1989
PainintheAS:

First of all, thank you for posting a very thorough topic discussion. Your self-conducted research is very valuable to others here. Because I live with someone who is a PhD in Biological Engineering and worked as a researcher and manager for a couple of Top 10 pharma companies, I know a few things from the other end of the aisle. Allow me to offer the following thoughts:

- There are plenty of research studies that noted promising outcomes in animals (usually: mice), only to turn out not to be effective in humans. Actually, even when a drug shows promise in humans with a real study, most will fail when it is put under more scrutiny. This is one of the reasons that pharma companies charge us outrageous prescription prices: They need to finance all failed drugs in the hunt of that one magic combination that will work. I'd just like to offer this view since you are choosing not to go on the available state-of-the-art treatment in the pursuit of a more experimental treatment.

- Considering the complexity and symbiosis of bacteria in our gut, in curiosity how do you determine:
a) This type of drug kills off the bacteria that do more harm than good?
b) The same bacteria won't return?
c) If yes to a) and b), the removal of bacteria will not cause other problems?
d) Are other bacteria or gut mechanisms involved in propelling spondylitis, if so, are those eliminated to?

- How are you benchmarking and following up your condition? Biomarkers? X-rays? Which efficacy does your experimental treatment show?

To me it seems that you are trying to fix the disease at the most upstream condition in the body, although not thoroughly researched or known. As you noted, the alternative is to turn off the problem downstream, with other possible side effects.

Since you started the treatment, which improvements have you noticed?

Thanks,
PsSpa_M_1989


Hey, really great reply. I plan to follow up with x-ray results and other metrics in the near future! However, there are some inaccuracies in what you've said. I mentioned some of these things before but maybe it just isn't clear because I write a lot, lol. I'll reply to each point.

1)
IBS is now clearly known to be marked by an imbalance in the intestinal flora. This imbalance has certain characteristic traits in certain diseases. Rifaximin IS APPROVED for IBS treatment. I have the same intestinal floral imbalance (skewed firmicutes to bacteroidetes ratio) as the rats transfected with HLA-B27. Rifaximin also immediately made my "sensation" of stress (which is related to cytokines and interleukins...you can read any recent paper on major depressive disorder or schizophrenia and find that the leakiness in the blood-brain barrier, versus the AS disease leakiness in the gut, exists. The same cytokines that cause inflammation in AS sufferers are the same cytokines that cause issues for those with these mental conditions.) This is because cytokines are responsible for both groups of people inducing a "stress/inflammation" response. You will find that many of the symptoms of "lethargy, lack of motivation, and exhaustion" can occur in severe cases of MDD. Why? They are both related to cytokine expression in some way.

2)
The bacteria CAN return. This is why it's important to try and remove, then outcompete them with proper strains that don't elicit an immune response in me (HLA-B27 genetics must be considered here.) This also explains why when I eat certain foods that are healthy for others (like certain fermented foods) I am permanently screwed after. The bacteria compete with the ones that I have so strongly that they start to take over. I will then NOT heal without antimicrobial intervention. This is the same thing that happened to me when I visited Mexico. My friend and I ate the same things, but I got sick because a) less mucosal membrane protection and b) far less diversity in my microbiota to handle the offense and outcompete the invader. It turned out what I was infected with happened to also be pathogenic for pretty much anyone but I could not fend it off.

3)
I mentioned studies where similar drugs were used IN HUMANS with great positive effect. Rifaximin is just one choice, there are others I mentioned that were tested in humans that brought down chemokine markers. I posted the studies here. Some of the studies have even stated directly that "it is now commonly accepted in research that AS is a disease of the gut (or periodontal.)" Those studies are posted here too. Whether or not every drug works in humans that works in mice is not really up for debate to me. I took Rifaximin, I immediately felt the "calm" that came with reduced cytokine expression. Did I test for it? No. I don't have a readily available method to do that without great expense. I can also go take a bunch of the other medications I've listed (and I am actually going to do that for experimental understanding and to try and address my Reactive Arthritis problem that accompanies a spectrum of issues I have related to HLA-B27 genetics.) However, I can tell you without a doubt, DRASTIC improvement using Rifaximin. I can digest better, I have less pain, and my lethargy and extreme sweating with minimal exertion have reduced (all signs of less stress response.) I will soon try to seek approval for Rifamycin as it has an effect that I think is necessary that Rifaximin doesn't, which is it can help heal intestinal cells in addition to the upregulating of tight-junction proteins.

4)
If there are other mechanisms of AS that Rifaximin/antibiotics won't treat (which there may very well be,) my research hasn't indicated much in the way of this. I still scour once a week to find out. The most CUTTING EDGE (2017-2019) research indicates it is a disease of intestinal permeability (makes sense, invaders making it into the bloodstream, just as they would in the mouth) and bacterial imbalance, either mediated by genetics or some offending event. Every member I spoke to here in the beginning of my post mentioned that their disease started after some "event" that was either pathogen from travel/food or periodontal in nature.

5)
The state-of-the-art treatments currently available clearly have side-effects that include death. Not really willing to risk infection, cancer, or death. Your body NEEDS to communicate via chemokines. Blocking them is unwise. I guarantee within 10 years, this approach currently being taken will be out the door. Doctors still prescribe NSAIDs to people with AS. My AS started becoming drastically worse after 2-3 days of taking a pain-reliever. I told the doctor prescribing me it that this would be the result and he said not to worry. The state of the art treatments START with NSAIDs and then work their way up to biologics. If a doctor can hand me something that is going to burn my intestinal lining away, I think I would rather take an approach that builds it back up, or brings things back to balance (which is what tests using Rifaximin have been shown to do in HUMAN IBS patients, not just rats. This is why it is approved for HUMANS.)

6)
Pharmacokinetics can affect the way the same drug operates in the same person. Which fillers are used varies from generic to a brand name and this causes people to have altered uptake of the medicine. Requirements for a generic medication to be okayed by the regulating agencies require the blood concentration to be something like 40% similar within a certain timeframe. I can't remember the exactly metric but remember reading it and thinking that this is LAUGHABLY ridiculous as the difference between the generic absorption and the brand name can be wildly different. So much so that the dose for one person in one drug could be completely different than what is required in the bloodstream. It's sheer madness to promote money-making opportunities for other companies to produce generics. On top of that, the reason pharmaceutical companies can charge so much for their drug is not quite as simple reasons as you claim. They pay other companies to "not compete" and create a generic equivalent. This can cost taxpayers up to 3.5 billion a year. Have a read about it (and many other lovely practices employed) here. LINK

--------

What's current in research labs is rarely what's current in a doctors office. Doctors are usually very behind and dogmatic. They stick to what they were taught in school when that was cutting-edge and don't keep up as often as they should. I've met a few doctors that do keep up and my goodness it is so much more relieving to talk to someone who continually hones their craft. Big pharma also has to charge a lot of money for other reasons. They line the pockets of specific doctors who tout their drug, versus other competing drugs, on the market. Here's JUST ONE example (Link). Many doctors have written articles about their guilt being so high that they had to start turning down these companies because the things they were told to regurgitate during medical conferences were actually quite questionable. I read a few articles to this tune. I've also been mistreated/misdiagnosed by doctors MULTIPLE times, simply because they didn't want to hear me out. This has to do with the general psychology of professional thinking that someone else can't have insight or perspective that might be informative. It is an issue with ego and I began to get tired of it causing me harm. I sought to help myself because I felt I was equipped enough to do so. I would like to note that my self-treatment has resulted in greater healing and benefit than ANYTHING a doctor has ever given to me, except the one I mentioned who "keeps up." That woman is truly a healer/doctor and "practices medicine" IMHO. Many doctors take the Hippocratic Oath to do no harm. But if you look at the number of misdiagnosis and deaths due to medicines and their side effects, coupled with their pockets being lined for pushing certain drugs, you can see that there is just really a lot of hypocrisy going around.

Now that I am feeling better enough to get back out in the world, I have applied for a Master's Degree in Machine Learning and Data Science, with an emphasis on early detection and prevention of disease. It is a growing movement and I plan to make changes and give alternatives to people so that they need to enter this wheelhouse of "take this drug you'll be ok." I also plan to be involved in genomics and microbiome analysis. They've already designed certain strains of bacteria to treat arthritis and other autoimmune conditions because the bacteria produce IL-10, a Th2 cytokine which promotes immune regulation and not inflammation. Other research has been done for arthritis in gene editing cells to produce anti-inflammatory molecules when stressed instead of the normal inflammatory molecules. These approaches will be vastly superior to taking drugs.
Posted By: PsSpa_M_1989

Re: Potential "Patch" for AS - 08/17/19 06:29 AM

Thanks again, for a very thorough response. I appreciate the opportunity to share thoughts with you and to tap into your knowledge of current research.

Originally Posted by PainintheAS
1)
IBS is now clearly known to be marked by an imbalance in the intestinal flora. This imbalance has certain characteristic traits in certain diseases. Rifaximin IS APPROVED for IBS treatment. I have the same intestinal floral imbalance (skewed firmicutes to bacteroidetes ratio) as the rats transfected with HLA-B27. Rifaximin also immediately made my "sensation" of stress (which is related to cytokines and interleukins...you can read any recent paper on major depressive disorder or schizophrenia and find that the leakiness in the blood-brain barrier, versus the AS disease leakiness in the gut, exists. The same cytokines that cause inflammation in AS sufferers are the same cytokines that cause issues for those with these mental conditions.) This is because cytokines are responsible for both groups of people inducing a "stress/inflammation" response. You will find that many of the symptoms of "lethargy, lack of motivation, and exhaustion" can occur in severe cases of MDD. Why? They are both related to cytokine expression in some way.


Did you find that the stress relief you experienced with Rifaximin, was similar to that of dietary intervention? Before I started a TNF-alpha inhibitor, I tried the Autoimmune Protocol for 30 days. My stressors were definetely severely hampered during this diet. The day I switched back to a standard diet I had a cup of coffee and a pastry in the morning (bike to work day..). Within a minute my body felt like it was going through a stress reaction, very strange feeling after a month of plants, salmon, shrimps, chicken, cassava root/coconut flour, coconut milk, tons of turmeric/ginger/garlic, and berries/occassional orange.

My ESR decreased from 32 to 30 and my CRP decreased from 22 mg/dL to 9 mg/dL with 30 days of the AIP-diet. Not back to normal ranges but possibly supporting your conclusion that harmful bacteria go into hibernation/starvation with diet-only are still able to proliferate (albeit with less intensity). I also don't know if my data set is sufficient to make any conclusions about this, however it is better than nothing.

I intend to post a thread within the next few months about my experience with NSAID, diets, biologics, chinese herbs (had no effect, even though many of them are supposed to suppress certain bacteria in the gut and bind to TNF-alpha, COX, various interleukins, etc. according to studies in animals: link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003708/), after about 10 months of trial-and-error since my diagnosis. My primary benchmark is ESR/CRP since they were both elevated at diagnosis and fluctuated with dietary interventions and medications.

Originally Posted by PainintheAS
2)
The bacteria CAN return. This is why it's important to try and remove, then outcompete them with proper strains that don't elicit an immune response in me (HLA-B27 genetics must be considered here.) This also explains why when I eat certain foods that are healthy for others (like certain fermented foods) I am permanently screwed after. The bacteria compete with the ones that I have so strongly that they start to take over. I will then NOT heal without antimicrobial intervention. This is the same thing that happened to me when I visited Mexico. My friend and I ate the same things, but I got sick because a) less mucosal membrane protection and b) far less diversity in my microbiota to handle the offense and outcompete the invader. It turned out what I was infected with happened to also be pathogenic for pretty much anyone but I could not fend it off.


To me, it seems a big challenge is how to identify the maintenance phase after you get rid of the bacteria? Given individual response to bacteria composition.

Originally Posted by PainintheAS
3)
I mentioned studies where similar drugs were used IN HUMANS with great positive effect. Rifaximin is just one choice, there are others I mentioned that were tested in humans that brought down chemokine markers. I posted the studies here. Some of the studies have even stated directly that "it is now commonly accepted in research that AS is a disease of the gut (or periodontal.)" Those studies are posted here too. Whether or not every drug works in humans that works in mice is not really up for debate to me. I took Rifaximin, I immediately felt the "calm" that came with reduced cytokine expression. Did I test for it? No. I don't have a readily available method to do that without great expense. I can also go take a bunch of the other medications I've listed (and I am actually going to do that for experimental understanding and to try and address my Reactive Arthritis problem that accompanies a spectrum of issues I have related to HLA-B27 genetics.) However, I can tell you without a doubt, DRASTIC improvement using Rifaximin. I can digest better, I have less pain, and my lethargy and extreme sweating with minimal exertion have reduced (all signs of less stress response.) I will soon try to seek approval for Rifamycin as it has an effect that I think is necessary that Rifaximin doesn't, which is it can help heal intestinal cells in addition to the upregulating of tight-junction proteins.

4)
If there are other mechanisms of AS that Rifaximin/antibiotics won't treat (which there may very well be,) my research hasn't indicated much in the way of this. I still scour once a week to find out. The most CUTTING EDGE (2017-2019) research indicates it is a disease of intestinal permeability (makes sense, invaders making it into the bloodstream, just as they would in the mouth) and bacterial imbalance, either mediated by genetics or some offending event. Every member I spoke to here in the beginning of my post mentioned that their disease started after some "event" that was either pathogen from travel/food or periodontal in nature.


What impact has Rifaximin had on your AS symptoms? If you have elevated ESR/CRP, that is a good way to keep tabs on your acute phase inflammation. Preferrably before and after Rifaximin.

My diagnosis is "axial psoriatic arhtritis" (axPsa, aka psoriatic spondylitis). I am HLA-B27 negative but I suspect I have the HLA-C06 allele since my psoriasis broke out when I was a child and my arthritis presented 12-15 years after that. I am not able to trace my psoriasis nor my psoriatic arhritis to a certain infection; however, my mother said that one of my early doctors believed my psoriasis was triggered by a strep throat. Psoriatic arthritis could be a latent feature of the same disease, the same way as some with autoimmune disorders have latent leukemia, lymphoma, etc. As a child I also had many other infections (including issues with # of white blood cells), apparently uncommonly many according to my mother, even for a child. My immune system appears to have overcompensated for that later in life, as I didn't have fever or a sick day in well over a decade. I'm 30 now.

Unfortunately, axPsa is much less known than both AS and pPsa, since only 5% of Psa patients present with this condition. In fact, researchers are only recently showing interest in studying axPsa. Consequently, a research agenda is still being debated by the authorities on the subejct:

https://ard.bmj.com/content/76/4/701
https://journals.lww.com/co-rheumat...dylitis_or_ankylosing_spondylitis.3.aspx

A part of the issue is that axPsa and AS appear to be on a spectrum. I.e., it may not be entirely clear whether someone has axial psoriatic arthritis or ankylosing spondylitis with psoriasis. When I look at the diagnostic criteria, I find myself somewhere in between. My age of onset was earlier than axPsa but later than AS. I am HLA-B27 negative but have sclerosis of my sacroiliac joint.

The reason I write all this, is that I wonder if axPsa and AS have the same causes? Did you come across anything to that effect in your research, or something that could inform my condition?

Originally Posted by PainintheAS
5)
The state-of-the-art treatments currently available clearly have side-effects that include death. Not really willing to risk infection, cancer, or death. Your body NEEDS to communicate via chemokines. Blocking them is unwise. I guarantee within 10 years, this approach currently being taken will be out the door. Doctors still prescribe NSAIDs to people with AS. My AS started becoming drastically worse after 2-3 days of taking a pain-reliever. I told the doctor prescribing me it that this would be the result and he said not to worry. The state of the art treatments START with NSAIDs and then work their way up to biologics. If a doctor can hand me something that is going to burn my intestinal lining away, I think I would rather take an approach that builds it back up, or brings things back to balance (which is what tests using Rifaximin have been shown to do in HUMAN IBS patients, not just rats. This is why it is approved for HUMANS.)

6)
Pharmacokinetics can affect the way the same drug operates in the same person. Which fillers are used varies from generic to a brand name and this causes people to have altered uptake of the medicine. Requirements for a generic medication to be okayed by the regulating agencies require the blood concentration to be something like 40% similar within a certain timeframe. I can't remember the exactly metric but remember reading it and thinking that this is LAUGHABLY ridiculous as the difference between the generic absorption and the brand name can be wildly different. So much so that the dose for one person in one drug could be completely different than what is required in the bloodstream. It's sheer madness to promote money-making opportunities for other companies to produce generics. On top of that, the reason pharmaceutical companies can charge so much for their drug is not quite as simple reasons as you claim. They pay other companies to "not compete" and create a generic equivalent. This can cost taxpayers up to 3.5 billion a year. Have a read about it (and many other lovely practices employed) here. LINK


Personally, I saw more effect with AIP than NSAID. So I agree that NSAID is not state-of-the-art. Biologics still to be determined for me but my biomarkers returned to normal within 5 weeks. Some studies suggest that biologics slow down and sometimes reverses mSASSS.

Regarding big pharma - it is a whole other discussion. It tends to become somewhat black/white. I have seen them from the other side though, they do good things too. America just has a stupid health care system that exacerbates businesses ability to take advantage of people.

I went through almost a half-year argument with myself whether I was going to start TNF-alpha inhibitors or not. The chance of getting a serious infection sometime during long-term treatment with biologics is very likely. It is almost a certain outcome if you look at the statistics. Cancer seems less certain, from the published data this far. However, these risks also exist in placebo groups to a surprising degree. As patients with automimmune diseases, we are already at elevated risk for infections and cancers. Biologics may lower another important risk factor: Cardiovascular events, a leading cause of premature death for individuals with chronic inflammation.

Here is the article library I used when deciding for biologics and which eventually helped me convince to start this treatment:

PSORIATIC ARTHRITIS MORTALITY ARTICLES

https://academic.oup.com/rheumatology/article/56/6/907/2965335
http://www.jrheum.org/content/37/9/1898
https://acrabstracts.org/abstract/mortality-rates-and-causes-in-psoriatic-arthritis-patients/
https://www.ncbi.nlm.nih.gov/pubmed/29947129
https://ard.bmj.com/content/73/1/149
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883139/
https://ard.bmj.com/content/64/suppl_2/ii14
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133459/
https://mauiderm.com/update-on-psoriatic-arthritis-and-the-focus-on-new-treatments/
https://academic.oup.com/rheumatology/article/58/1/80/5077390
https://synapse.koreamed.org/DOIx.php?id=10.4078/jrd.2018.25.3.197&vmode=PUBREADER

VACCINATIONS

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080407/
http://www.ibdclinic.ca/treatment/m...at-checks-will-i-need-before-i-start-it/
https://www.uspharmacist.com/articl...ng-disease-modifying-antirheumatic-drugs
https://ard.bmj.com/content/76/2/414

PSORIATIC ARTHRITIS HUMIRA SIDE EFFECTS / LONG TERM STUDIES EFFECTIVENESS

https://clinicaltrials.gov/ct2/show/results/NCT01111240
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574748/
https://www.centerforbiosimilars.co...es-for-patients-with-psoriatic-arthritis

PSORIATIC ARHTRITIS TREATMENT

https://journals.sagepub.com/doi/10.1177/2475530318812244

COMBORBIDITES

https://www.jmcp.org/doi/full/10.18553/jmcp.2018.17421

NON-PUBLIC ARTICLES

Cardiovascular morbidity and mortality Liew 2019
Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis Lehtinen 1993
Early psoriatic arthritis: short symptom duration, male gender, and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up (Theander 2012)

Originally Posted by PainintheAS
What's current in research labs is rarely what's current in a doctors office. Doctors are usually very behind and dogmatic. They stick to what they were taught in school when that was cutting-edge and don't keep up as often as they should. I've met a few doctors that do keep up and my goodness it is so much more relieving to talk to someone who continually hones their craft. Big pharma also has to charge a lot of money for other reasons. They line the pockets of specific doctors who tout their drug, versus other competing drugs, on the market. Here's JUST ONE example


In my opinion, yes and no. My rheumatologist is out of med school within the last 10 years (likely speaks to your point) and she is somewhat open to dietary interventions. I will ask her about your hypothesis. I think most doctors try to keep up by way of conferences and collegial work. Many may not do in-depth research but most are at least committed to their patients.

My main critique of doctors are their lack of imagination and foresight. They always react to symptoms and rarely seem to bother with preventive care. For all the dermatologists I met over the last 15 years, no one ever told me that I am at higher risk for cardiovascular problems and cancers, nor that diet can be very helpful. All I learned about my risk factors and dietary benefits, I learned myself. If I knew this I would have adjusted my S-A-D diet much earlier than I did!

Originally Posted by PainintheAS
Many doctors have written articles about their guilt being so high that they had to start turning down these companies because the things they were told to regurgitate during medical conferences were actually quite questionable.


Yes this most likely influences which medication they prescribe too. I.e. if AbbVie takes you out for trips and fancy dinners you are probably more likely to advocate Humira over Enbrel, Cimzia or Cosentyx.

Originally Posted by PainintheAS
I read a few articles to this tune. I've also been mistreated/misdiagnosed by doctors MULTIPLE times, simply because they didn't want to hear me out. This has to do with the general psychology of professional thinking that someone else can't have insight or perspective that might be informative. It is an issue with ego and I began to get tired of it causing me harm. I sought to help myself because I felt I was equipped enough to do so. I would like to note that my self-treatment has resulted in greater healing and benefit than ANYTHING a doctor has ever given to me, except the one I mentioned who "keeps up." That woman is truly a healer/doctor and "practices medicine" IMHO. Many doctors take the Hippocratic Oath to do no harm. But if you look at the number of misdiagnosis and deaths due to medicines and their side effects, coupled with their pockets being lined for pushing certain drugs, you can see that there is just really a lot of hypocrisy going around.


Misdiagnosis is definitely a problem. Also: lack of knowledge/insight. My GP didn't seem to know psoriatic arthritis was a disease, when I presented with psoriasis and stiff neck. She relied on specialists to make the diagnosis. The experiences you had could also be a problem of hiearchy; the doctor is supposed to be an authority and if the patient starts asking uncomfortable questions that redefines the hiearchy, it becomes threatening for the person who values to uphold the authority. Curious patients should not be an issue for doctors who care more for the patients' wellbeing than their doctor's license.

Originally Posted by PainintheAS
Now that I am feeling better enough to get back out in the world, I have applied for a Master's Degree in Machine Learning and Data Science, with an emphasis on early detection and prevention of disease. It is a growing movement and I plan to make changes and give alternatives to people so that they need to enter this wheelhouse of "take this drug you'll be ok." I also plan to be involved in genomics and microbiome analysis. They've already designed certain strains of bacteria to treat arthritis and other autoimmune conditions because the bacteria produce IL-10, a Th2 cytokine which promotes immune regulation and not inflammation. Other research has been done for arthritis in gene editing cells to produce anti-inflammatory molecules when stressed instead of the normal inflammatory molecules. These approaches will be vastly superior to taking drugs.


Good job and good luck. Remember that drugs are supposed to make us feel better and manage our conditions. We all have to make our decisions on how to get better.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/20/19 08:44 AM

Great post! So many articles here (some I've read) and others I'll dig into. I actually have 12 tabs open with some fresh material related to HLA-B27 that I wanted to dig into. I haven't gotten it all together in a concise format, so I'll write another post on it later. There's actually some good stuff in it (related to your question about other metabolites.) When you mentioned it, I decided to start doing some digging. It actually ended up giving me a very positive lead (something easy to take that can easy the inflammation significantly [yes in rats, lol].) The gist was that out of 530'ish metabolites, over half were profoundly skewed from healthy controls. Supplementation with propionate (and somewhere else I read butyrate) is what normalized a lot of the inflammation by attenuating these differences in metabolites. I knew butyrate would do this, and I have taken it before, and recently theorized that propionate may be good to supplement as I've been making my L. reuteri yogurt. I was choosing between multiple fibers to use for the starter culture to use as a fermentable source when I came across partially hydrolyzed guar gum (PHGG.) From my readings on making yogurt with wheat dextrin, PHGG, and inulin...PHGG had a significantly elevated production of propionate. I have made a few batches of the yogurt so far and am working on getting the texture to the proper/pleasing point. The L. reuteri yogurt has a very calming effect on me within 10-15 minutes of eating it. I haven't been able to be consistent with it for a number of reasons but I plan to start making it more consistently soon.

For the TNF-alpha blockers, I have gone through a struggle mentally for a long time too. Many studies showed me that, in the long run, they don't truly address some of the major concerns in the disease. The second thing, and it's a big one, is that while you may be correct about being at higher risk for cancer as an autoimmune sufferer, my entire family (father's side) has had cancer and died from it. With that double-whammy, I am not willing to risk it.

A heads up about the next post I am going to write:

I've dug deep down into a bunch of other articles and I've found quite a bit. While a lot of it relates to HLA-B27, one of the papers I read demonstrates that the gene only affects disease onset and not burden. So, HLA-B27 or not, I believe the things that potentiate the disease are very similar amongst all sufferers. HLA-B27 can just bring you there much quicker due to its alterations of the gut and the interaction thereof. Having said that:

1) There are some other supplements to consider that have not yet been mentioned anywhere I've seen on this forum. I'll be posting them with the associated studies where I found them.

2) Rifamycin can be used in a polyarticular injection routine. The fascinating find was that this seemed to also calm axial symptoms (the injections are being done in the major joints around the body but not the spine.) This opens up a bunch of possibilities as to what is going on. I'll be linking that soon.

3) My pain in my intestines is located in the lower ileum. This is the hallmark symptom for HLA-B27 sufferers. I was able to find an article that showed Paneth cells near this region produce cRAMP (cathelicidin-related AMP.) This is a substance that is antibacterial to many gram-positive bacteria. I had, in the recent past, taken Ample shakes (keto shakes with very good macros) which contained probiotics as well. I instantly started to feel sweat, tired, and tons more back pain. Most of the bacteria listed are gram-positive in that shake. My theory is that because of the altered immune response to bacteria and increased cRAMP, the lower ileum becomes a war zone. You can't take probiotics and expect that since they are good for most people (my friend is now drinking it and is doing just fine) that they will be good for HLA-B27 individuals. My body is definitely trying to attack things in that area and that's where my pain always has been. That was the FIRST area to be relieved when I first started taking Rifaximin. So, in essence...you are correct. Determining proper maintenance after antimicrobials is going to prove very challenging. Random thought: If we can gene edit all these mice/bacteria for testing...we should just be creating strains of bacteria that evade the interactions with our immune system instead of trying to find drugs to stop the immune cascade. I can imagine tailoring an entire set of bacteria for each location in the body that a) still provides the proper function that normal individuals have, but b) doesn't elicit an immune response to either its metabolites or the LPS cell-coating. This, to me, seems like something we should be doing by now.

4) I am on an off phase of Rifaximin (for reasons of purging any bacterial strains that have gain tolerance, which is mentioned in the literature.) The tolerance is quickly lost. So, I will be going back on it in about 2 weeks. Of course, I ate some things as a test, like you, and the pain started coming back. Some things can make me react quickly, as you mentioned, and others take time. However, I've tried taking curcumin supplements in the past (at the recommended dosage) with no effect. Frustrated, I decided to take much more of the supplement this time around. I'm glad I did this. I had a very similar sensation to that of Rifaximin. So, I did some digging and there is a TON of information out there on updated delivery methods and encapsulation technologies. The supplement I had was AOR's Curcumin Ultra, which uses CurQFen technology. Curcumin and its metabolites/derivatives work on ALL the pathways we are concerned with for AS. My sweating, fatigue, and pain all diminished. I stopped taking it, the pain came back. I took it two days later, and the same sensation. These were merely SINGLE doses. I have just purchased a few other brands to test around and see what works best in my system. Given that it targets TNF-alpha and various chemokines, I am quite hopeful that this, in addition to what I mentioned I've found in 1 above, will be a very powerful non-drug way to deal with this disease. As a bonus, I had much better digestion after taking the pills, too (also claimed to be a benefit of turmeric/curcumin.)

5) There have been some peptide therapies created in some studies that help the HLA-B27 molecule properly fold, thus reducing homodimer formation, significantly. Others have gone about it a different way with antigens that target specific forms of B27 as it begins to accumulate in the endoplasmic reticulum so that it cannot form homodimers/heterotrimers. I like the idea of using a peptide to create a proper fold at the proper rate instead of antigens that address the issue downstream after the creation of some of these "junk" molecules. There are some other cases of different MHC Class I molecules creating heavy chain dimers (I think it was HLA-A02, but I can't remember.) Also, they were able to demonstrate these compounds can be formed in cells at 26 C (far below normal biological levels) but this COULD explain why certain individuals get arthritic pain in cold weather, specifically in joints where blood flow is reduced and temperature can drop drastically. The main reason HLA-B27 misfolds is because of a) unique locations of Cys (I believe at the 67th position) and also Lys (around 130) and b) the slow rate of folding due to these highly rare amino acids at these locations. So, cold temperatures effectively slow down the folding process of non-B27 MHC Class I molecules as well. Whether they actually lead to arthritogenic properties afterward, I do not know. This was just a theory about cold weather and joint pain.

6) I've looked into Sulfasalazine as an option. Much like Rifaximin, it is anti-inflammatory in the gut (it's just the Rifaximin also has antimicrobial properties as well as upregulates tight junction proteins, so that's why I went that route.) However, what I read recently, and didn't know prior) is that Sulfasalazine also drastically reduces homdimer formation in HLA-B27 individuals. This definitely makes me consider using it, should these other routes I mentioned above not work.
Posted By: Winston

Re: Potential "Patch" for AS - 08/20/19 02:37 PM

Since you seem so data-driven, you should look more closely at the TNF-a drug/cancer link. Doctors have not seen in clinical practice the cancers predicted based on the clinical trial data. Twenty+ years on from those trials, this has led researchers to speculate that it was the underlying disease process, rather than the drugs, that caused the cancers that prompted the black-box warnings. Another wrinkle: The cancers linked to TNF-a drugs are, for the most part, blood and immune system cancers. (Skin cancer is another big one, but that's easily monitored for). As more and more data comes out linking other, more common sorts of cancers (e.g., lung cancer, breast cancer, colon cancer) to chronic inflammation, researchers are talking amongst themselves about the possibility that drugs like TNF-a drugs may actually reduce a person's risk for those more common cancers. So the conclusion "my father's family had cancer so I shouldn't take these drugs" is overly simplistic.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/20/19 06:04 PM

I merely stated that I am not going to take the risk, not that I know for a fact that this will cause a problem. Everything we talk about here is currently our "best guess" speculation. The rates of infection ARE higher for those on TNF-alpha drugs. The cancer stuff, we don't know. I won't chance it until what you claim is PROVEN. It's just a gamble I'm not willing to take.
Posted By: Winston

Re: Potential "Patch" for AS - 08/21/19 08:24 PM

That's fine, of course, so long as you acknowledge you're gambling by not taking the drugs as well.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/22/19 10:30 AM

Originally Posted by Winston
Since you seem so data-driven, you should look more closely at the TNF-a drug/cancer link. Doctors have not seen in clinical practice the cancers predicted based on the clinical trial data. Twenty+ years on from those trials, this has led researchers to speculate that it was the underlying disease process, rather than the drugs, that caused the cancers that prompted the black-box warnings. Another wrinkle: The cancers linked to TNF-a drugs are, for the most part, blood and immune system cancers. (Skin cancer is another big one, but that's easily monitored for). As more and more data comes out linking other, more common sorts of cancers (e.g., lung cancer, breast cancer, colon cancer) to chronic inflammation, researchers are talking amongst themselves about the possibility that drugs like TNF-a drugs may actually reduce a person's risk for those more common cancers. So the conclusion "my father's family had cancer so I shouldn't take these drugs" is overly simplistic.


Originally Posted by Winston
That's fine, of course, so long as you acknowledge you're gambling by not taking the drugs as well.


First off, I'd like to mention that when I posit something on this forum, I back it up with evidence. Usually a ton of it. The very drugs you suggest I take were only found to be "effective" by making data-driven decisions. So, I am not sure why someone wouldn't want to be data-driven, because that's how the people are treating you are ultimately behaving. I've never heard someone in here telling me to go take butter to treat my AS...likely because there is no data to support it. Secondarily, you suggest that I should look it up instead of providing me studies that demonstrate your point...which doesn't seem in the spirit of wanting to truly help me. But...I took the bait and looked it up for myself. Link

In short, the article concludes that the warning for these drugs is valid, as those who have NHL cancers were nearly two-fold more likely to be users of TNF-inhibiting drugs. Not only that, etanercept was over two times more likely to be associated with NHL cancers. This is in a study of 55,446 adult patients in insurance databases.

So, this brings me to the following:

1) Why must I acknowledge anything to you? Why are you trying to get me to prove I'm risking my life by not putting a foreign substance into my bloodstream?

All my choices are to bring my levels of TNF-alpha down through methods that don't require things entering into my bloodstream. Surely this would have a similar effect to a dose-dependent blockage, too. However, the less systemic route I propose attenuates the signals instead of hitting them with hammers and blunting them. There are MANY other ways to reduce TNF-alpha besides taking anti-TNF drugs. They happen to be the topic of my next post I mentioned I wanted to write in my prior post.

2) You mention that the doctors aren't seeing the types of cancer in clinical practice that the studies suggest.

I'd say this study begs to differ, for one. A second question would be: what doctors are you talking about? Can you provide me anything, like I constantly provide people here...that has a leg to stand on? I'm not trying to be rude but your response almost feels like you simply don't like me...and because of that...you want me to feel like I'm making bad choices by not following yours (or a more standard approach,) since I like data so much.

3) This study was a roundup of patient data from quite a large range of time, ending in 2018.

Note, it only looked at NHL cancers. Perhaps there are even other forms of cancer that this drug can predispose people to. This would mean than two times more likely is just the floor, and the only direction is up.

4) TNF being "tumor necrosis factor" means it has the potential to destroy cancer cells.

It's only its relationship to NF-kB and JNK that determines whether the cell will undergo apoptosis or not. In HLA-B27 individuals, the signaling pathways that normally (through TNF-alpha) would induce apoptosis become cross-linked with NF-kB (which is largely responsible for cell survival.) Link This has to do with the odd homodimer formations that HLA-B27 undergoes. This would not be the same for all AS sufferers. Not taking genetics into account and making a broad generalization about the link between anti-TNF drugs and cancer would be unwise. In MY case, reducing TNF-alpha likely would reduce cancer induced by THAT modality...sure...

5) ...but you do have higher rates of infection with these drugs.

This is not questioned and many members have mentioned this side-effect. More infections, more inflammation, and then you're right back to an increased risk of cancer because of inflammation and cell damage caused by foreign invaders. This is because inflammation is defense, and dropping your defenses (even if they are a little hyperactive or functioning in conjunction with cell-survival chemokines) is NOT a good answer. Inflammation will still end up being created one way or another, and bacteria, virii, etc. all have the ability to translocate their genetic code into mine. This happens a lot in the gut, as likely these areas require many genes to be upregulated and downregulated to create a nice environment for bacteria and fungi to survive (as well as modulate my immune system, as is required to develop a proper-functioning immune system in the first place [symbiosis].) However, the rest of my body, like major organs and my respiratory tract...not as much. Hence why I am trying ways to reduce this pathway and not block it. The other thing I am trying to do is reduce homodimer formation so that NF-kB is not accidentally being included in the inflammation pathway (promoting cell survival and conferring some risk as you mention.) Sulfasalazine is noted to have homodimer formation reducing effects in HLA-B27 individuals. On the topic of TNF-alpha...either way, damned if I do and damned if I don't. So, I arrive, once again, at "I think not putting artificial chemicals into my bloodstream" being a wiser choice than "opening myself up to infectious agents and increased cancer through reduced ability to even cause inflammation in the first place AND having a chemical that shouldn't be there floating around."

6) Since anti-TNF drugs are used for more than just AS, but in many diseases of inflammation, it would seem to me that blocking inflammation is what increases one's risk for cancer when using anti-TNF drugs.

That's why the study I mention looks at all anti-TNF-using patients and not just those suffering from one form of disease. I'd like to point out that I did find studies that mention that there is no greater risk of "recurrence" in those who have already had cancer (or who have PsA,) which is a completely different topic altogether.

7) Given that the effectiveness of anti-TNF drugs usually diminishes with time and, in a few studies I've read, is really most effective when caught in early disease stages...I stand by my assessment of being safer not messing with my chemokine communication pathways.

My next post will have a lot of good options for people to consider in order to reduce intestinal permeability significantly, ameliorate the metabolite imbalance in HLA-B27 guts through some very simple supplements (backed up by studies of course,) increasing FOXP3+ T-Cells with another compound found in nature (backed up by studies for those with HLA-B27,) and some very interesting relationships between curcumin and it's action against the TNF-alpha / NF-kB (and other) inflammation pathways. I am having astounding success while on my break from Rifaximin with the newer (post-Bioperine) curcumin formulations.

8) Since you mentioned the types in practice not being the types predicted in studies, I thought you'd find this interesting.

Another study would indicate otherwise. Link. Corroborated by another study (the kidney connection being related to medications taken) Link. However, the way that HLA-B27 affects the disease in Asian populations is different than the way it is in Caucasian populations. As such, I was able to find one study that mentions a link to cancer but that this was more representative of the situation in Taiwan and that Asian populations are more at risk for malignancy Link 1 & Link 2. One of the studies goes on to state that the correlation was not found in Caucasian populations. Data is important when talking about risk to one group versus another.

------

In closing, I'm trying to help people the best way I know how to. I am digging, scouring, presenting, theorizing, experimenting, taking notes, and doing write-ups for others to benefit from someday (I hope.) If you also care, I'd much appreciate it if, like PsSpa_M_1989, you set me down the same path from which you are getting your information from...instead of leaving it up to me to find what you're claiming. We are ALL trying to heal here. Given how much reading I am already doing, and have done in hopes of helping myself and others, it would be nice if the person who started off claiming I was a data-lover actually provided me with data. I would feel much more like that person genuinely wanted to help me and not like that person was trying to criticize me for making alternative choices with a different opinion on risk management/aversion. I also can not and will not admit to gambling by not taking the drug, both by what I've presented here and the fact that it would require more hard evidence on your side to prove it to me in a rigorous manner. Otherwise, we can all do each other much more harm than good.

Posted By: PsSpa_M_1989

Re: Potential "Patch" for AS - 08/23/19 02:24 AM

PainintheAS:

I am about to go on vacation for a couple of weeks (will be on an airplane tomorrow night - with face mask! just in case someone is carrying a virus), will be happy to follow-up in a couple of weeks again on our previous discussion points.

By then, I can share some additional personal reflection on this, especially as it pertains to your concern with cancer. The excerpt below is from my Rx folder from AbbVie regarding Lymphoma and Leukemia for Humira:

"In the controlled portions of 39 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS, and UV, 2 lymphomas occurred among 7973 HUMIRA-treated patients vs 1 among 4848 control-treated patients. In 52 global controlled and uncontrolled clinical trials of HUMIRA, the observed rate of lymphomas was approximately 0.11 per 100 patient-years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race). [---] Patients with RA and other chronic inflammatory diseases, particularly those with high disease activity and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers."

Here is also the annex for the European Medicines Agency's approval of HUMIRA:
https://www.ema.europa.eu/en/documents/product-information/humira-epar-product-information_en.pdf

In deciding to go for the treatment, I found it to be more of an objective view of the risks and benefits.

Of course, if the treatment you currently have stop the disease, you will not need Humira!

I am hoping that I can get through 1-2 years on Humira w/o any side effects. Then I will feel comfortable with staying on these type of drugs for a longer period of time. If I can do ~5 years of biologics, and have arrested the disease to progress, then maybe at that time the selective JAK inhibitors are proven to be safe and effective? One can hope.

My own theory is that cancer primarily hits patients with pre-existing (slow-growing cancer), as I don't think adalimumab on its own is cancerogenic? It would imply that Humira is making it harder for your body to fight the cancer but does not "cause it"? Maybe with good lifestyle choices you can also reduce your risk of cancer.

Here are some recent research articles I read, regarding the effectiveness of Humira, to keep my spirit up:
https://ard.bmj.com/content/68/6/922
https://academic.oup.com/rheumatology/article/54/7/1210/1850347
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074727/

I do look forward to your next post! Also if you have additional research on axPsa that you came across, I would be eager to take part of it.

Thanks,
PsSpa_M_1989
Posted By: Caturday

Re: Potential "Patch" for AS - 08/24/19 11:56 PM

Originally Posted by PsSpa_M_1989
Thanks again, for a very thorough response. I appreciate the opportunity to share thoughts with you and to tap into your knowledge of current research.

Originally Posted by PainintheAS
1)
IBS is now clearly known to be marked by an imbalance in the intestinal flora. This imbalance has certain characteristic traits in certain diseases. Rifaximin IS APPROVED for IBS treatment. I have the same intestinal floral imbalance (skewed firmicutes to bacteroidetes ratio) as the rats transfected with HLA-B27. Rifaximin also immediately made my "sensation" of stress (which is related to cytokines and interleukins...you can read any recent paper on major depressive disorder or schizophrenia and find that the leakiness in the blood-brain barrier, versus the AS disease leakiness in the gut, exists. The same cytokines that cause inflammation in AS sufferers are the same cytokines that cause issues for those with these mental conditions.) This is because cytokines are responsible for both groups of people inducing a "stress/inflammation" response. You will find that many of the symptoms of "lethargy, lack of motivation, and exhaustion" can occur in severe cases of MDD. Why? They are both related to cytokine expression in some way.


Did you find that the stress relief you experienced with Rifaximin, was similar to that of dietary intervention? Before I started a TNF-alpha inhibitor, I tried the Autoimmune Protocol for 30 days. My stressors were definetely severely hampered during this diet. The day I switched back to a standard diet I had a cup of coffee and a pastry in the morning (bike to work day..). Within a minute my body felt like it was going through a stress reaction, very strange feeling after a month of plants, salmon, shrimps, chicken, cassava root/coconut flour, coconut milk, tons of turmeric/ginger/garlic, and berries/occassional orange.

My ESR decreased from 32 to 30 and my CRP decreased from 22 mg/dL to 9 mg/dL with 30 days of the AIP-diet. Not back to normal ranges but possibly supporting your conclusion that harmful bacteria go into hibernation/starvation with diet-only are still able to proliferate (albeit with less intensity). I also don't know if my data set is sufficient to make any conclusions about this, however it is better than nothing.

I intend to post a thread within the next few months about my experience with NSAID, diets, biologics, chinese herbs (had no effect, even though many of them are supposed to suppress certain bacteria in the gut and bind to TNF-alpha, COX, various interleukins, etc. according to studies in animals: link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003708/), after about 10 months of trial-and-error since my diagnosis. My primary benchmark is ESR/CRP since they were both elevated at diagnosis and fluctuated with dietary interventions and medications.

Originally Posted by PainintheAS
2)
The bacteria CAN return. This is why it's important to try and remove, then outcompete them with proper strains that don't elicit an immune response in me (HLA-B27 genetics must be considered here.) This also explains why when I eat certain foods that are healthy for others (like certain fermented foods) I am permanently screwed after. The bacteria compete with the ones that I have so strongly that they start to take over. I will then NOT heal without antimicrobial intervention. This is the same thing that happened to me when I visited Mexico. My friend and I ate the same things, but I got sick because a) less mucosal membrane protection and b) far less diversity in my microbiota to handle the offense and outcompete the invader. It turned out what I was infected with happened to also be pathogenic for pretty much anyone but I could not fend it off.


To me, it seems a big challenge is how to identify the maintenance phase after you get rid of the bacteria? Given individual response to bacteria composition.

Originally Posted by PainintheAS
3)
I mentioned studies where similar drugs were used IN HUMANS with great positive effect. Rifaximin is just one choice, there are others I mentioned that were tested in humans that brought down chemokine markers. I posted the studies here. Some of the studies have even stated directly that "it is now commonly accepted in research that AS is a disease of the gut (or periodontal.)" Those studies are posted here too. Whether or not every drug works in humans that works in mice is not really up for debate to me. I took Rifaximin, I immediately felt the "calm" that came with reduced cytokine expression. Did I test for it? No. I don't have a readily available method to do that without great expense. I can also go take a bunch of the other medications I've listed (and I am actually going to do that for experimental understanding and to try and address my Reactive Arthritis problem that accompanies a spectrum of issues I have related to HLA-B27 genetics.) However, I can tell you without a doubt, DRASTIC improvement using Rifaximin. I can digest better, I have less pain, and my lethargy and extreme sweating with minimal exertion have reduced (all signs of less stress response.) I will soon try to seek approval for Rifamycin as it has an effect that I think is necessary that Rifaximin doesn't, which is it can help heal intestinal cells in addition to the upregulating of tight-junction proteins.

4)
If there are other mechanisms of AS that Rifaximin/antibiotics won't treat (which there may very well be,) my research hasn't indicated much in the way of this. I still scour once a week to find out. The most CUTTING EDGE (2017-2019) research indicates it is a disease of intestinal permeability (makes sense, invaders making it into the bloodstream, just as they would in the mouth) and bacterial imbalance, either mediated by genetics or some offending event. Every member I spoke to here in the beginning of my post mentioned that their disease started after some "event" that was either pathogen from travel/food or periodontal in nature.


What impact has Rifaximin had on your AS symptoms? If you have elevated ESR/CRP, that is a good way to keep tabs on your acute phase inflammation. Preferrably before and after Rifaximin.

My diagnosis is "axial psoriatic arhtritis" (axPsa, aka psoriatic spondylitis). I am HLA-B27 negative but I suspect I have the HLA-C06 allele since my psoriasis broke out when I was a child and my arthritis presented 12-15 years after that. I am not able to trace my psoriasis nor my psoriatic arhritis to a certain infection; however, my mother said that one of my early doctors believed my psoriasis was triggered by a strep throat. Psoriatic arthritis could be a latent feature of the same disease, the same way as some with autoimmune disorders have latent leukemia, lymphoma, etc. As a child I also had many other infections (including issues with # of white blood cells), apparently uncommonly many according to my mother, even for a child. My immune system appears to have overcompensated for that later in life, as I didn't have fever or a sick day in well over a decade. I'm 30 now.

Unfortunately, axPsa is much less known than both AS and pPsa, since only 5% of Psa patients present with this condition. In fact, researchers are only recently showing interest in studying axPsa. Consequently, a research agenda is still being debated by the authorities on the subejct:

https://ard.bmj.com/content/76/4/701
https://journals.lww.com/co-rheumat...dylitis_or_ankylosing_spondylitis.3.aspx

A part of the issue is that axPsa and AS appear to be on a spectrum. I.e., it may not be entirely clear whether someone has axial psoriatic arthritis or ankylosing spondylitis with psoriasis. When I look at the diagnostic criteria, I find myself somewhere in between. My age of onset was earlier than axPsa but later than AS. I am HLA-B27 negative but have sclerosis of my sacroiliac joint.

The reason I write all this, is that I wonder if axPsa and AS have the same causes? Did you come across anything to that effect in your research, or something that could inform my condition?

Originally Posted by PainintheAS
5)
The state-of-the-art treatments currently available clearly have side-effects that include death. Not really willing to risk infection, cancer, or death. Your body NEEDS to communicate via chemokines. Blocking them is unwise. I guarantee within 10 years, this approach currently being taken will be out the door. Doctors still prescribe NSAIDs to people with AS. My AS started becoming drastically worse after 2-3 days of taking a pain-reliever. I told the doctor prescribing me it that this would be the result and he said not to worry. The state of the art treatments START with NSAIDs and then work their way up to biologics. If a doctor can hand me something that is going to burn my intestinal lining away, I think I would rather take an approach that builds it back up, or brings things back to balance (which is what tests using Rifaximin have been shown to do in HUMAN IBS patients, not just rats. This is why it is approved for HUMANS.)

6)
Pharmacokinetics can affect the way the same drug operates in the same person. Which fillers are used varies from generic to a brand name and this causes people to have altered uptake of the medicine. Requirements for a generic medication to be okayed by the regulating agencies require the blood concentration to be something like 40% similar within a certain timeframe. I can't remember the exactly metric but remember reading it and thinking that this is LAUGHABLY ridiculous as the difference between the generic absorption and the brand name can be wildly different. So much so that the dose for one person in one drug could be completely different than what is required in the bloodstream. It's sheer madness to promote money-making opportunities for other companies to produce generics. On top of that, the reason pharmaceutical companies can charge so much for their drug is not quite as simple reasons as you claim. They pay other companies to "not compete" and create a generic equivalent. This can cost taxpayers up to 3.5 billion a year. Have a read about it (and many other lovely practices employed) here. LINK


Personally, I saw more effect with AIP than NSAID. So I agree that NSAID is not state-of-the-art. Biologics still to be determined for me but my biomarkers returned to normal within 5 weeks. Some studies suggest that biologics slow down and sometimes reverses mSASSS.

Regarding big pharma - it is a whole other discussion. It tends to become somewhat black/white. I have seen them from the other side though, they do good things too. America just has a stupid health care system that exacerbates businesses ability to take advantage of people.

I went through almost a half-year argument with myself whether I was going to start TNF-alpha inhibitors or not. The chance of getting a serious infection sometime during long-term treatment with biologics is very likely. It is almost a certain outcome if you look at the statistics. Cancer seems less certain, from the published data this far. However, these risks also exist in placebo groups to a surprising degree. As patients with automimmune diseases, we are already at elevated risk for infections and cancers. Biologics may lower another important risk factor: Cardiovascular events, a leading cause of premature death for individuals with chronic inflammation.

Here is the article library I used when deciding for biologics and which eventually helped me convince to start this treatment:

PSORIATIC ARTHRITIS MORTALITY ARTICLES

https://academic.oup.com/rheumatology/article/56/6/907/2965335
http://www.jrheum.org/content/37/9/1898
https://acrabstracts.org/abstract/mortality-rates-and-causes-in-psoriatic-arthritis-patients/
https://www.ncbi.nlm.nih.gov/pubmed/29947129
https://ard.bmj.com/content/73/1/149
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883139/
https://ard.bmj.com/content/64/suppl_2/ii14
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133459/
https://mauiderm.com/update-on-psoriatic-arthritis-and-the-focus-on-new-treatments/
https://academic.oup.com/rheumatology/article/58/1/80/5077390
https://synapse.koreamed.org/DOIx.php?id=10.4078/jrd.2018.25.3.197&vmode=PUBREADER

VACCINATIONS

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080407/
http://www.ibdclinic.ca/treatment/m...at-checks-will-i-need-before-i-start-it/
https://www.uspharmacist.com/articl...ng-disease-modifying-antirheumatic-drugs
https://ard.bmj.com/content/76/2/414

PSORIATIC ARTHRITIS HUMIRA SIDE EFFECTS / LONG TERM STUDIES EFFECTIVENESS

https://clinicaltrials.gov/ct2/show/results/NCT01111240
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574748/
https://www.centerforbiosimilars.co...es-for-patients-with-psoriatic-arthritis

PSORIATIC ARHTRITIS TREATMENT

https://journals.sagepub.com/doi/10.1177/2475530318812244

COMBORBIDITES

https://www.jmcp.org/doi/full/10.18553/jmcp.2018.17421

NON-PUBLIC ARTICLES

Cardiovascular morbidity and mortality Liew 2019
Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis Lehtinen 1993
Early psoriatic arthritis: short symptom duration, male gender, and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up (Theander 2012)

Originally Posted by PainintheAS
What's current in research labs is rarely what's current in a doctors office. Doctors are usually very behind and dogmatic. They stick to what they were taught in school when that was cutting-edge and don't keep up as often as they should. I've met a few doctors that do keep up and my goodness it is so much more relieving to talk to someone who continually hones their craft. Big pharma also has to charge a lot of money for other reasons. They line the pockets of specific doctors who tout their drug, versus other competing drugs, on the market. Here's JUST ONE example


In my opinion, yes and no. My rheumatologist is out of med school within the last 10 years (likely speaks to your point) and she is somewhat open to dietary interventions. I will ask her about your hypothesis. I think most doctors try to keep up by way of conferences and collegial work. Many may not do in-depth research but most are at least committed to their patients.

My main critique of doctors are their lack of imagination and foresight. They always react to symptoms and rarely seem to bother with preventive care. For all the dermatologists I met over the last 15 years, no one ever told me that I am at higher risk for cardiovascular problems and cancers, nor that diet can be very helpful. All I learned about my risk factors and dietary benefits, I learned myself. If I knew this I would have adjusted my S-A-D diet much earlier than I did!

Originally Posted by PainintheAS
Many doctors have written articles about their guilt being so high that they had to start turning down these companies because the things they were told to regurgitate during medical conferences were actually quite questionable.


Yes this most likely influences which medication they prescribe too. I.e. if AbbVie takes you out for trips and fancy dinners you are probably more likely to advocate Humira over Enbrel, Cimzia or Cosentyx.

Originally Posted by PainintheAS
I read a few articles to this tune. I've also been mistreated/misdiagnosed by doctors MULTIPLE times, simply because they didn't want to hear me out. This has to do with the general psychology of professional thinking that someone else can't have insight or perspective that might be informative. It is an issue with ego and I began to get tired of it causing me harm. I sought to help myself because I felt I was equipped enough to do so. I would like to note that my self-treatment has resulted in greater healing and benefit than ANYTHING a doctor has ever given to me, except the one I mentioned who "keeps up." That woman is truly a healer/doctor and "practices medicine" IMHO. Many doctors take the Hippocratic Oath to do no harm. But if you look at the number of misdiagnosis and deaths due to medicines and their side effects, coupled with their pockets being lined for pushing certain drugs, you can see that there is just really a lot of hypocrisy going around.


Misdiagnosis is definitely a problem. Also: lack of knowledge/insight. My GP didn't seem to know psoriatic arthritis was a disease, when I presented with psoriasis and stiff neck. She relied on specialists to make the diagnosis. The experiences you had could also be a problem of hiearchy; the doctor is supposed to be an authority and if the patient starts asking uncomfortable questions that redefines the hiearchy, it becomes threatening for the person who values to uphold the authority. Curious patients should not be an issue for doctors who care more for the patients' wellbeing than their doctor's license.

Originally Posted by PainintheAS
Now that I am feeling better enough to get back out in the world, I have applied for a Master's Degree in Machine Learning and Data Science, with an emphasis on early detection and prevention of disease. It is a growing movement and I plan to make changes and give alternatives to people so that they need to enter this wheelhouse of "take this drug you'll be ok." I also plan to be involved in genomics and microbiome analysis. They've already designed certain strains of bacteria to treat arthritis and other autoimmune conditions because the bacteria produce IL-10, a Th2 cytokine which promotes immune regulation and not inflammation. Other research has been done for arthritis in gene editing cells to produce anti-inflammatory molecules when stressed instead of the normal inflammatory molecules. These approaches will be vastly superior to taking drugs.


Good job and good luck. Remember that drugs are supposed to make us feel better and manage our conditions. We all have to make our decisions on how to get better.


I have the same disease progression as your axial psoriatic arthritis and I have bilateral damage to my joints. I've had a stiff neck for years and have had psoriasis since I was 10 years old but I was born premature by 3 months.... stayed in the hospital for another 3 months and was not breastfed. Then I got mono at age 6... so my gut microbiome is not very diverse to begin with and my genetic snps also points to me not having a diverse gut microbiome so I will follow this thread closely as perhaps can help people dealing with our specific issues.

I'm contemplating taking humira or cosentyx in order to deal with my axial issues. Thanks for the posts it's been very helpful.
Posted By: Caturday

Re: Potential "Patch" for AS - 08/25/19 12:03 AM

Originally Posted by PainintheAS
Originally Posted by PsSpa_M_1989
PainintheAS:

First of all, thank you for posting a very thorough topic discussion. Your self-conducted research is very valuable to others here. Because I live with someone who is a PhD in Biological Engineering and worked as a researcher and manager for a couple of Top 10 pharma companies, I know a few things from the other end of the aisle. Allow me to offer the following thoughts:

- There are plenty of research studies that noted promising outcomes in animals (usually: mice), only to turn out not to be effective in humans. Actually, even when a drug shows promise in humans with a real study, most will fail when it is put under more scrutiny. This is one of the reasons that pharma companies charge us outrageous prescription prices: They need to finance all failed drugs in the hunt of that one magic combination that will work. I'd just like to offer this view since you are choosing not to go on the available state-of-the-art treatment in the pursuit of a more experimental treatment.

- Considering the complexity and symbiosis of bacteria in our gut, in curiosity how do you determine:
a) This type of drug kills off the bacteria that do more harm than good?
b) The same bacteria won't return?
c) If yes to a) and b), the removal of bacteria will not cause other problems?
d) Are other bacteria or gut mechanisms involved in propelling spondylitis, if so, are those eliminated to?

- How are you benchmarking and following up your condition? Biomarkers? X-rays? Which efficacy does your experimental treatment show?

To me it seems that you are trying to fix the disease at the most upstream condition in the body, although not thoroughly researched or known. As you noted, the alternative is to turn off the problem downstream, with other possible side effects.

Since you started the treatment, which improvements have you noticed?

Thanks,
PsSpa_M_1989


Hey, really great reply. I plan to follow up with x-ray results and other metrics in the near future! However, there are some inaccuracies in what you've said. I mentioned some of these things before but maybe it just isn't clear because I write a lot, lol. I'll reply to each point.

1)
IBS is now clearly known to be marked by an imbalance in the intestinal flora. This imbalance has certain characteristic traits in certain diseases. Rifaximin IS APPROVED for IBS treatment. I have the same intestinal floral imbalance (skewed firmicutes to bacteroidetes ratio) as the rats transfected with HLA-B27. Rifaximin also immediately made my "sensation" of stress (which is related to cytokines and interleukins...you can read any recent paper on major depressive disorder or schizophrenia and find that the leakiness in the blood-brain barrier, versus the AS disease leakiness in the gut, exists. The same cytokines that cause inflammation in AS sufferers are the same cytokines that cause issues for those with these mental conditions.) This is because cytokines are responsible for both groups of people inducing a "stress/inflammation" response. You will find that many of the symptoms of "lethargy, lack of motivation, and exhaustion" can occur in severe cases of MDD. Why? They are both related to cytokine expression in some way.

2)
The bacteria CAN return. This is why it's important to try and remove, then outcompete them with proper strains that don't elicit an immune response in me (HLA-B27 genetics must be considered here.) This also explains why when I eat certain foods that are healthy for others (like certain fermented foods) I am permanently screwed after. The bacteria compete with the ones that I have so strongly that they start to take over. I will then NOT heal without antimicrobial intervention. This is the same thing that happened to me when I visited Mexico. My friend and I ate the same things, but I got sick because a) less mucosal membrane protection and b) far less diversity in my microbiota to handle the offense and outcompete the invader. It turned out what I was infected with happened to also be pathogenic for pretty much anyone but I could not fend it off.

3)
I mentioned studies where similar drugs were used IN HUMANS with great positive effect. Rifaximin is just one choice, there are others I mentioned that were tested in humans that brought down chemokine markers. I posted the studies here. Some of the studies have even stated directly that "it is now commonly accepted in research that AS is a disease of the gut (or periodontal.)" Those studies are posted here too. Whether or not every drug works in humans that works in mice is not really up for debate to me. I took Rifaximin, I immediately felt the "calm" that came with reduced cytokine expression. Did I test for it? No. I don't have a readily available method to do that without great expense. I can also go take a bunch of the other medications I've listed (and I am actually going to do that for experimental understanding and to try and address my Reactive Arthritis problem that accompanies a spectrum of issues I have related to HLA-B27 genetics.) However, I can tell you without a doubt, DRASTIC improvement using Rifaximin. I can digest better, I have less pain, and my lethargy and extreme sweating with minimal exertion have reduced (all signs of less stress response.) I will soon try to seek approval for Rifamycin as it has an effect that I think is necessary that Rifaximin doesn't, which is it can help heal intestinal cells in addition to the upregulating of tight-junction proteins.

4)
If there are other mechanisms of AS that Rifaximin/antibiotics won't treat (which there may very well be,) my research hasn't indicated much in the way of this. I still scour once a week to find out. The most CUTTING EDGE (2017-2019) research indicates it is a disease of intestinal permeability (makes sense, invaders making it into the bloodstream, just as they would in the mouth) and bacterial imbalance, either mediated by genetics or some offending event. Every member I spoke to here in the beginning of my post mentioned that their disease started after some "event" that was either pathogen from travel/food or periodontal in nature.

5)
The state-of-the-art treatments currently available clearly have side-effects that include death. Not really willing to risk infection, cancer, or death. Your body NEEDS to communicate via chemokines. Blocking them is unwise. I guarantee within 10 years, this approach currently being taken will be out the door. Doctors still prescribe NSAIDs to people with AS. My AS started becoming drastically worse after 2-3 days of taking a pain-reliever. I told the doctor prescribing me it that this would be the result and he said not to worry. The state of the art treatments START with NSAIDs and then work their way up to biologics. If a doctor can hand me something that is going to burn my intestinal lining away, I think I would rather take an approach that builds it back up, or brings things back to balance (which is what tests using Rifaximin have been shown to do in HUMAN IBS patients, not just rats. This is why it is approved for HUMANS.)

6)
Pharmacokinetics can affect the way the same drug operates in the same person. Which fillers are used varies from generic to a brand name and this causes people to have altered uptake of the medicine. Requirements for a generic medication to be okayed by the regulating agencies require the blood concentration to be something like 40% similar within a certain timeframe. I can't remember the exactly metric but remember reading it and thinking that this is LAUGHABLY ridiculous as the difference between the generic absorption and the brand name can be wildly different. So much so that the dose for one person in one drug could be completely different than what is required in the bloodstream. It's sheer madness to promote money-making opportunities for other companies to produce generics. On top of that, the reason pharmaceutical companies can charge so much for their drug is not quite as simple reasons as you claim. They pay other companies to "not compete" and create a generic equivalent. This can cost taxpayers up to 3.5 billion a year. Have a read about it (and many other lovely practices employed) here. LINK

--------

What's current in research labs is rarely what's current in a doctors office. Doctors are usually very behind and dogmatic. They stick to what they were taught in school when that was cutting-edge and don't keep up as often as they should. I've met a few doctors that do keep up and my goodness it is so much more relieving to talk to someone who continually hones their craft. Big pharma also has to charge a lot of money for other reasons. They line the pockets of specific doctors who tout their drug, versus other competing drugs, on the market. Here's JUST ONE example (Link). Many doctors have written articles about their guilt being so high that they had to start turning down these companies because the things they were told to regurgitate during medical conferences were actually quite questionable. I read a few articles to this tune. I've also been mistreated/misdiagnosed by doctors MULTIPLE times, simply because they didn't want to hear me out. This has to do with the general psychology of professional thinking that someone else can't have insight or perspective that might be informative. It is an issue with ego and I began to get tired of it causing me harm. I sought to help myself because I felt I was equipped enough to do so. I would like to note that my self-treatment has resulted in greater healing and benefit than ANYTHING a doctor has ever given to me, except the one I mentioned who "keeps up." That woman is truly a healer/doctor and "practices medicine" IMHO. Many doctors take the Hippocratic Oath to do no harm. But if you look at the number of misdiagnosis and deaths due to medicines and their side effects, coupled with their pockets being lined for pushing certain drugs, you can see that there is just really a lot of hypocrisy going around.

Now that I am feeling better enough to get back out in the world, I have applied for a Master's Degree in Machine Learning and Data Science, with an emphasis on early detection and prevention of disease. It is a growing movement and I plan to make changes and give alternatives to people so that they need to enter this wheelhouse of "take this drug you'll be ok." I also plan to be involved in genomics and microbiome analysis. They've already designed certain strains of bacteria to treat arthritis and other autoimmune conditions because the bacteria produce IL-10, a Th2 cytokine which promotes immune regulation and not inflammation. Other research has been done for arthritis in gene editing cells to produce anti-inflammatory molecules when stressed instead of the normal inflammatory molecules. These approaches will be vastly superior to taking drugs.


I've tried to get my hands on this antibiotic drug you've mentioned in order to try it on myself. But no doctor will give me it even doctors on the roadback.org so how are you able to get these prescribed to you?
Posted By: PainintheAS

Re: Potential "Patch" for AS - 08/26/19 05:16 AM

Caturday:

Not sure if you saw it mentioned before but this drug is currently also prescribed for IBS, IBS-D, and HE. Given that AS shares overlap with IBS I played up the IBS angle. I also found someone who happened to have some leftover pills to try before I went to the gastroenterologist and told him about my theory for Rifaximin...that I actually tried it (illegally at first,) and that it worked. He sent off the "prior auth" to insurance and it got approved. You can't ask for it in order to treat AS directly. I walked into my gastro with all the papers that were relevant (mainly the ones from my first post about rifaximin in mice treating AS.) I also came in with a few others printed out. He seemed impressed and had no argument to offer up. I'd recommend this route for anyone who has gut involvement.

Hope this helps!
Posted By: PsSpa_M_1989

Re: Potential "Patch" for AS - 09/17/19 04:25 AM

PainintheAS:

I am back from vacation now and had an appointment with my rheumatologist when I came back. She did not reject the idea of "leaky gut" and certain bacteria being involved with AS. She also did not reject the idea that Rifaximin can kill off those bacteria. Also, she said the Rifaximin is prescribed by some "functional doctors" but not by regular doctors without GI-symptoms (which you mentioned).

That being said, I am curious how your trial is going? Are you symptom free? Does your doctors check ESR, CRP, or serum IgA to find out if your disease is currently active?

Thanks,
PsSpa_M_1989
Posted By: Mary Beth

Re: Potential "Patch" for AS - 09/21/19 04:41 PM

I may add more later but it’s important to stress that there is serious doubt as to whether the use of TNF blockers increases cancer risk; the most common results I’ve seen indicate that it’s likely RA itself, and not the treatment, that raises risks. To be certain we would need to give these medications to large numbers of people who do NOT have underlying diseases, over many years, and compare them to matched controls. This will NEVER happen.

Quote
our review finds a consistent lack of association between TNFi and cancer across the 11 papers included.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241884/#!po=0.819672
Posted By: Mary Beth

Re: Potential "Patch" for AS - 09/21/19 08:28 PM

I want to thank you for your detailed posts.

My own thought is that the microbiome plays an enormous role in our overall health. It is undoubtedly influenced by diet, exposure, antibiotic use, genetic makeup, environment, and all sorts of other things that we barely understand.

My guess is that exposure (or lack of exposure) to pathogens and parasites also plays a role.

That said, we understand so very little about it and messing about with antibiotic protocols or extreme diets is to take part in a self-prescribed science experiment. The problem with antibiotic protocols is that resistance develops fairly rapidly and so they would need to be rotated. They are not a “cure” in that we do not understand what causes our own microbiomes to develop and change over time to begin with, so we can take short-term actions to radically alter them but we don’t know what will cause them to change back after that, or what they will change back to. Will it be better? Worse?

I am negative for the particular genetic marker that is most associated with AS in caucasians so I’m not sure what that means either, and remember that the high correlation between HLA B27 and AS is, firstly, primarily in caucasians and, secondly, while most with AS are positive, most with the genetic marker do NOT have AS. So we know very little about cause and effect here.

I have had 14 years of mostly positive experience with the biologics and so I am biased in their favor. I did have one very scary virus that I thought might kill me but, I have no way of knowing how that would have played out without Humira.
Posted By: Caturday

Re: Potential "Patch" for AS - 09/22/19 08:20 PM

He did provide some great info with his hypothesis though. I still can't find a doctor to prescribe me this. They all think it's very risky despite the studies I have shown them.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 09/28/19 07:01 PM

Originally Posted by PsSpa_M_1989
PainintheAS:

I am back from vacation now and had an appointment with my rheumatologist when I came back. She did not reject the idea of "leaky gut" and certain bacteria being involved with AS. She also did not reject the idea that Rifaximin can kill off those bacteria. Also, she said the Rifaximin is prescribed by some "functional doctors" but not by regular doctors without GI-symptoms (which you mentioned).

That being said, I am curious how your trial is going? Are you symptom free? Does your doctors check ESR, CRP, or serum IgA to find out if your disease is currently active?

Thanks,
PsSpa_M_1989


Not symptom-free, but doing MUCH better. I have some theories as to why this may be the case and I've been so busy that I have not had time to do my long post with updates. I will try to get around to doing that soon. For those tests, I'll be getting them soon. I had X-Rays but they only showed some disc degeneration, they didn't allow me to have an MRI. Since my disease is in "early stages" X-Rays are often unrevealing as the damage that would be evident hasn't formed yet. Currently, my pain is in the enthesis and I doubt it has caused much bone destruction/formation.


Originally Posted by Mary Beth
I may add more later but it’s important to stress that there is serious doubt as to whether the use of TNF blockers increases cancer risk; the most common results I’ve seen indicate that it’s likely RA itself, and not the treatment, that raises risks. To be certain we would need to give these medications to large numbers of people who do NOT have underlying diseases, over many years, and compare them to matched controls. This will NEVER happen.

Quote
our review finds a consistent lack of association between TNFi and cancer across the 11 papers included.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241884/#!po=0.819672


I'll read your paper but I provided some links that showed that TNF alpha usage had some links in Caucasians (to cancer) but not to Asians. I posted those links earlier. While I agree that it's hard to separate whether it was the disease or the drug, the TYPES of cancer indicated that it was LIKELY the drug (kidney cancers, etc.) I'll read your paper after work today just to see the date (if it was before or after the ones I've posted) and what their conclusions were.


Originally Posted by Mary Beth
I want to thank you for your detailed posts.

My own thought is that the microbiome plays an enormous role in our overall health. It is undoubtedly influenced by diet, exposure, antibiotic use, genetic makeup, environment, and all sorts of other things that we barely understand.

My guess is that exposure (or lack of exposure) to pathogens and parasites also plays a role.

That said, we understand so very little about it and messing about with antibiotic protocols or extreme diets is to take part in a self-prescribed science experiment. The problem with antibiotic protocols is that resistance develops fairly rapidly and so they would need to be rotated. They are not a “cure” in that we do not understand what causes our own microbiomes to develop and change over time to begin with, so we can take short-term actions to radically alter them but we don’t know what will cause them to change back after that, or what they will change back to. Will it be better? Worse?

I am negative for the particular genetic marker that is most associated with AS in caucasians so I’m not sure what that means either, and remember that the high correlation between HLA B27 and AS is, firstly, primarily in caucasians and, secondly, while most with AS are positive, most with the genetic marker do NOT have AS. So we know very little about cause and effect here.

I have had 14 years of mostly positive experience with the biologics and so I am biased in their favor. I did have one very scary virus that I thought might kill me but, I have no way of knowing how that would have played out without Humira.


While you might be correct that we know very little about the microbiome's TOTAL role in the body and all the links it has to health, immunity, and cellular function...if you read many papers on AS and the microbiome...at the research level, it is basically agreed upon unilaterally that this is a disease of a) host response to specific cytokines being aberrant, b) in the case of HLA-B27 individuals the earlier onset of AS is related to the fact that the homodimers that HLA-B27 forms cause binding to cytokines that normally aren't reactive when a PROPER heterotrimer is formed by HLA (non-B27) molecules in other individuals. This homodimer, which is created by misfolding due to the fact that HLA-B27 folds slowly, can express itself on the cell surface (binding to things it shouldn't) and promote RAMPANT inflammatory processes, of which the intestines are a source of that inflammation. The slow degradation of the gut mucosal membrane, along with the aberrant inflammatory process, causes bacterial imbalances that further reinforce the cycle of cytokine and interleukin up-regulation, which code for more inflammatory cytokines. ALL of this has been taken from the articles that I have posted. To note, I didn't post something if I couldn't find at least 2 articles that supported the same conclusion. The number of articles I've read versus the number I've posted on this forum is in a ratio of over 10:1.

To reiterate: Rifaximin DOES NOT form very many resistant bacteria. By nature of the way it works, which I won't go into, this is just a property of that drug. Any bacteria that do gain resistance were shown to lose the resistance VERY quickly. I made sure of all these things before taking rifaximin to begin with. Rifaximin is also one of the MOST SAFE antibiotics as it is NOT systemic. It will not find its way into other parts of your body as it only acts locally, as an antibiotic, anti-inflammatory, and an up-regulator of detox pathways. This makes it an IDEAL candidate for SAFE usage without forming any scary critters or doing any real harm to your body unless you happen to be allergic.

I will also reiterate that I posted a paper that we are all so concerned about affecting our microbiomes by using antibiotics, when all the other drugs like NSAIDS, Biologics, Diabetes Medications, etc ALL affect the microbiome and can even cause these bacteria to become resistant to antibiotics and other chemicals. I've proposed that my methodology is better than these other medications because AT LEAST I am affecting ONLY what I intended to, without other fallout. You cannot say this about ANY other medication to treat disease as they all have "fallout." I've considered very carefully what I am doing and the risk factors and I have experienced NO real side effects or issues from taking rifaximin. I usually react quite poorly to antibiotics due to the fact that I have extremely sensitive (ie thin and damaged) gut lining, due to HLA-B27. I took rifaximin to reduce inflammation and to address the microbial imbalances.

The REASON most people with HLA-B27 don't have the disease is that it's not a disease conferred by the gene. It's a disease that the gene makes you more susceptible to due to the increased gut damage that is done to individuals with HLA-B27. You still would need a triggering event to cause the disease process to begin. Almost everyone I've spoken to on here, as well as myself, all began to have symptoms after either a periodontal issue or an intestinal issue (traveling bug, etc.) There is more to say but it's all too complex to lay down in one post.

Originally Posted by Caturday
He did provide some great info with his hypothesis though. I still can't find a doctor to prescribe me this. They all think it's very risky despite the studies I have shown them.


Thanks! I recommend you keep trying, as I had to, to find another doc who would be sympathetic. Some people are still in the dark, don't know that rifaximin is NOT risky compared to other medications, or just don't respond well to you being well-informed...it somehow is an insult to their "intelligence" or "time spent in academia/practicing." I've had to battle this quite a bit and it took me many tries to find the right doctor. Just keep trying is all I can say. It's worth it!
Posted By: PainintheAS

Re: Potential "Patch" for AS - 09/29/19 02:47 AM

I've gone back and dug through my papers on the cancer link. This one says the cancers developed are in the same pattern as NSAID usage (meaning the drugs being taken are what are causing the increased risk in AS patients.) Biologics may not exactly be the same as NSAIDS but this could be seen as a baseline for AS patients because they will be taking lots of drugs in the NSAID class, as well as biologics. Good to know what's going on with the NSAID's Link

Your study happened to be conducted in 2012, so relatively recent. However, the studies I posted were in 2016 and 2017 and are related to the risk rates for AS patients compared to healthy controls. Link 1 & Link 2. What we can infer from these studies is that the AS disease does seem to POSSIBLY have some link to cancer but only in Asian populations. The rates were not significant from healthy controls in European patients. Both studies confirmed this.

This allows us to do some analysis. Those with AS don't have an increased risk of cancer, likely. However, those taking NSAID's do, particularly in the organs associated with the processing and clearing of drugs from the body. Makes sense. Looking at the data for biologics a lot of studies are mentioning that TNFi is not linked to cancer. However, I've read things like "the rate of cancer was not much higher" in the same journal. This means that the rate was, indeed, higher. One thing we have to make clear is that TNF can play both sides. It can be anti-cancer and it can be cancer-promoting. This depends on its interaction with NF-kB, which promotes cell survival. So, for HLA-B27+ individuals, TNF-alpha is definitely something you'd want to block as it can interact with NF-kB in an aberrant fashion...which would then leave a damaged cell alive (not undergoing apoptosis) allowing for cancer to take hold. The question is then...well if the rates of those with cancer are not higher in AS patients (as shown in Links 1 & 2 above) then why are studies being conducted across multiple disease types (that use biologics) in order to determine the cancer risk of TNFi therapy. People keep mentioning that cancer is increased in those with AS (that it's the disease that caused these cancers not the drug.) However, we can now say that it's really not the disease...so what is it? If you're taking drugs, which are blocking cell signals...I'd put my money on that. To go one step further, and provide you with a study that does indicate a link (and did a very good job of separating people from the study who had already had a cancer, or formed cancer after the trial) then check this out. Link One might claim that reducing inflammation with TNFi is going to reduce cancer risks without question. Let's assume this is correct...I'm ok with that. Then, we must also consider that chronic infections are listed in many trials as being extremely elevated in those who use biologics. This ALSO makes sense. But wait, if you're having more infections all the time...then you are experiencing more inflammation...which can lead to cancer. Food for thought!
Posted By: achala

Re: Potential "Patch" for AS - 10/29/19 06:31 PM

Originally Posted by PainintheAS
Great post! So many articles here (some I've read) and others I'll dig into. I actually have 12 tabs open with some fresh material related to HLA-B27 that I wanted to dig into. I haven't gotten it all together in a concise format, so I'll write another post on it later. There's actually some good stuff in it (related to your question about other metabolites.) When you mentioned it, I decided to start doing some digging. It actually ended up giving me a very positive lead (something easy to take that can easy the inflammation significantly [yes in rats, lol].) The gist was that out of 530'ish metabolites, over half were profoundly skewed from healthy controls. Supplementation with propionate (and somewhere else I read butyrate) is what normalized a lot of the inflammation by attenuating these differences in metabolites. I knew butyrate would do this, and I have taken it before, and recently theorized that propionate may be good to supplement as I've been making my L. reuteri yogurt. I was choosing between multiple fibers to use for the starter culture to use as a fermentable source when I came across partially hydrolyzed guar gum (PHGG.) From my readings on making yogurt with wheat dextrin, PHGG, and inulin...PHGG had a significantly elevated production of propionate. I have made a few batches of the yogurt so far and am working on getting the texture to the proper/pleasing point. The L. reuteri yogurt has a very calming effect on me within 10-15 minutes of eating it. I haven't been able to be consistent with it for a number of reasons but I plan to start making it more consistently soon.


I would be interested to hear the update on the above:

1. Butyrate, how is that going? Have you tried Butycaps (tributyrin) by any chance? I have seen couple of article linking production of Butyrate to L. Rhamnosus (enhancing Roseburia & Blautia), see below links.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597169/#R67
https://www.ncbi.nlm.nih.gov/pubmed/26394008
Also Grass Fed Animal Butter supply approx 300mg daily intake of butyrate (+ cold potatos).
These guys are saying Clostridia clusters IV and XIVa produce Butyrate but did not find the right supplier for me yet:
https://www.ncbi.nlm.nih.gov/pubmed/24226770

2. Propionate. I understood that delivering sodium propionate directly led to kidney inflammation in some subjects. Inulin indicated (as a feed) as long chains that boost F. prausnitzii - immune regulating bacteria. However, we find that FOS & inulin also feeds Klebsiella & E. coli that are particularly problematic in spondyloarthritis:
https://www.ncbi.nlm.nih.gov/pubmed/9351217
On the top of that:
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2006.03186.x

"Fructan ingestion in rats has been associated with elevated epithelial proliferation and excessive mucin release (suggesting epithelial injury and irritation),55 and with increased mucus production, epithelial permeability and susceptibility to experimental salmonella colitis.57 Furthermore, ingestion of arabinoxylans, likely to contain xylo‐oligosaccharides, also induces epithelial injury and increased susceptibility to carcinogens.58 FOS also promotes apoptosis of colonic epithelial cells in a model of acute DNA injury,59 an effect that might be beneficial in the prevention of neoplasia but detrimental in a patient with colitis"

Which brings me to FODMAPs and Fructose malabsorption problem, that apparently 1 in 3 people with IBS are prone to.

3. Guar Gum suppose to grow Bifidus but there is some conflicting evidence been found as well:
https://www.ncbi.nlm.nih.gov/pubmed/10607504

so yes, I am quite curious how is it going...
I am becoming more & more convinced that the first flare of uveitis coincided with Helicobacter pylori treatment with 2 antibiotics + an additional drug dont remember which one, at that time in 2017 .... i mean happened 1 week after the treatment...
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/08/19 10:45 PM

Ok, everyone...sorry for the extended time period between updates. However, I have been very busy with a new job to pay for all of the expenses I incurred in my downtime from surgery/sickness. A brief update about me, before my updates about everything else:

My coverage for Rifaximin was dropped, as the FDA guidelines allow for 1 initial batch and 2 refills as a limit. I reached that limit and am now fighting with my insurance through grievance/appeals processes (with the help of my GI and his assistant.) I was never 100% free from pain but I was around 80-90% better. My mobility/flexibility was much improved. I could sit in chairs for long periods of time with little-to-no pain. About 1.5-2 weeks after stopping Rifaximin, my pain is significantly worse. I felt it ramping up slowly, and it probably took this long because of the other things I've added to my regimen, which comprise the rest of this message (my update.) So here ya all go.

-------------------------------------------------------------------------------------
The yogurt never came to proper consistency based on multiple trials. I then found a friend with another yogurt maker and did everything as I thought was correct between both yogurt makers at the same time. In conclusion, my yogurt maker is faulty. I have sent in for a replacement. So, updates in the future on that.

Now, here comes quite a lengthy list of things I have been reading about, all very interesting:

1)
Loss of Dendritic Cells (modulate tolerance to "self".) It is the loss of a specific population of dendritic cells that allow tolerance to self-antigens in lymphatic tissue, particularly mesenteric lymph nodes, found throughout the gut that can be attributed to things going "haywire." There's more in this paper about enhanced IL-17 production from the CD4 T-cells, but this is nothing new. I think this paints a clearer picture of how the immune system gets distorted and how important it is to normalize what's going on in the gut.
Link

Further support for how this shaping occurs:
Link

Guess where there is also a large clustering of lymph nodes? You guessed it, right where most of the major regions of pain are for SpA's that relate to the sacroiliac/lumbar regions. Check out this image that demonstrates where the intestinal lymph is drained:
Link

So, the intestinal inflammation comes from the loss of resistance to self, and begins in the gut in the specialized gut lymph nodes. These nodes, then get inflamed, promote aberrant immune cell priming, and then you have both intestinal leakage and an aberrantly tuned immune system. If your gut inflammation is severe enough, then things from the gut will leak into the bloodstream and cause reactions as many studies have already shown (eg. link to Klebsiella, Yersinia, etc.) However, this would also describe why CARBS causes a problem, even in people with no Klebsiella. This is because carbs (as shown in my first post) create immune complexes. If you've lost tolerance for self-antigens due to the loss of dendritic cells, you'll likely react to the carbs that other individuals would have "tolerance" for. In essence, you are attacking pretty much everything because of the loss of dendritic cells. After that, it's just a slow degradation process that erodes and changes the rest of the immune response in many different ways, given your genetics and lifestyle choices.

The other modality of inflammation has already been discussed, which is the upregulation in cytokine/interleukin profiles, which are mediated by the imbalance in the gut (mainly relevant for HLA-B27+ individuals.) For HLA-B27+ individuals, both the above loss of dendritic cells + the change in cytokine expression are going to accelerate the path to the disease state. In those that are NOT HLA-B27+, either an extended period of time with gut imbalance or a breach of the immune system by a foreign invader (periodontal causes mentioned many times,) or a course of damaging drugs (like NSAIDs or antibiotics,) can start this inflammatory cascade...though it would take longer.

This leads me to...

2)
Skullcap (more importantly the compound baicalein found in skullcap) upregulates around 20 different tight junction proteins. Using this in conjunction with rifaximin had AMAZING effects for me. Also, since the gut barrier is very similar to the blood-brain barrier, I referred my friend to start taking skullcap since he has been having issues with a leaky BBB and depressive/anhedonic behaviors. He also perceived incredible results, however, he did get withdrawal symptoms once it wore off (and he gets that with almost everything that modulates either neurotransmitters or inflammation/cytokine profile. His neurological imbalance requires more study on GABA/Glutamate and other cell-signaling mechanics to fully understanding, but it also looks like there is an analog to the loss of dendritic cells in the gut in his case, which would be the loss of astrocytes and microglia for glutamate reuptake after the molecule is first bound to the presynaptic terminal. Interesting parallels!
Link

3)
Turmeric/Curcumin has a variety of effects on various chemical pathways, most notably TNF-alpha activated NF-kB signaling, which is activated by LPS (lipopolysaccharide) coatings of bacteria in the immune system. I've talked about both of these in earlier posts, and TNF-alpha blockers are used to help with AS, so we know this is highly relevant. It also has mood-elevating effects, as well as anti-depressive effects. New generations of curcumin/turmeric supplements are leaving behind the Bioperine-enhanced absorption modality for either nano-emulsion (tween, which is polysorbate-80,) gamma-dextrin (a sugar ring that encapsulates the turmeric and is absorbed in the small intestine,) and lipid-bound delivery methodologies. These new formulations are Meriva, Longvida, Theracurmin, C3/C3-Reduct (which is a high dose of either all 3 of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, or tetrahydrocurcumin (THC) for C3-reduct [I believe],) and a few others. These were the main players for the newer generation of delivery techniques. I have not tried any of these mentioned except for Theracurmin and the gamma-dextrin bound formulations because I believe the other methods of administration have issues related to the heart (lipid-bound molecules can lead to the production of TMAO, which can cause heart issues) or intestinal inflammation (tween [polysorbate 80] delivery method). I decided to try CurQFen and CurcuWin, both having significant short term effects on my pain management while I have been on and off of Rifaximin. These are a great additive to any regimen as they support reducing inflammation to healthy levels. Here is some supporting evidence:
Link
Link
Link

4)
Berberine (found in a few different plants, with berberis aristatis being the most common) is purported to have a variety of positive effects. Mood, blood sugar, lipid, and inflammation seem most notable. It functions similarly to curcumin but with far more wide-reaching effects. There are actually far more beneficial effects, but it seems that similar to turmeric/curcumin, NF-kB signaling is affected, which will downregulate the inflammation caused by LPS coatings from bacteria, as well as a few other modalities of inducing inflammation.
Link
Link

5)
Propionate/Butyrate was mentioned before, but proper ratios are hard to pin down. To respond to the above post, I have tried Tributyrin but felt some pain after using it. Not sure if that was coincidental, however, I have decided that using direct metabolites of bacteria or other processes in the body is often a recipe for disaster. I want to affect the things higher up in the chain so that the production of butyrate is normalized (not normalize it myself.) I think butyrate production is something that should vary with time, based on demand, and the gut microbiome homeostasis is something that dynamically adapts to modulate this. I have tried regular butyrate too and noticed I felt very ill for a short period of time after doing so. Not sure exactly what was going on, however, this is because there is a sweet zone for these metabolites, and too much can impair the gut barrier and proper crypt-depth. I think I may have posted on that before. So, my method of recovery will be related to altering the gut microbiome, increasing tight-junction proteins via rifaximin and skullcap, as well as all of the other benefits rifaximin has to offer (I have procured a non-doctor source until I can get it approved by my insurance again.)
-------------------------------------------------------------------------------------

In my humble opinion, I believe I have found strong enough links that describe each and every step of the process of pathogenesis, including why the specific sites of the spine are attacked, of this disease. I have demonstrated that taking rifaximin has helped me (and others via prior posts,) and that the cessation of its use has caused me to revert to prior symptomologies. I will also provide ANOTHER study that shows that Rifamycin, the parent molecule for Rifaximin, is also better at reducing inflammation AND is reported as SIGNIFICANTLY effective in the management of AS (also in a paper that demonstrates periodontal pathogens can be responsible for AS symptoms.) Here you go:
Link
Link

There's a lot more I've been looking into and a lot more supporting evidence for why tolerance to self is lost but I think that's outside the scope of what I am trying to do here. I probably have another 20 papers you all could read related to FOXP3+ T-cells, and how baicalein can help. I've also found studies that show T-Cells lose memory for what they are normally supposed to do under inflammatory conditions and then become pathogenic, etc.

I've found my stack/regimen that works for me. I am now going to be contacting the man who cured himself in an attempt to spread awareness about this disease and how to treat it. If you read the story of this man, you will find many similar parallels to what's going on here, though his situation was more dire (Castleman Disease.) He's gone on to use a drug that already existed and was prescribed for other conditions in order to treat his own, saving his life in the process. His paying attention to clues that doctors said were irrelevant resembles my own experience quite closely. I'd like to find a way to collaborate with him, and the organization he helped found, the CDCN (Castleman Disease Collaborative Network.) He is also now partnered with the Chan-Zuckerberg "Rare as One" organization, which aims to eradicate diseases. I want to reach out to both David Fajgenbaum and to CZI in order to see if they have ways to help me improve the medical understanding/cohesiveness of various researchers in AS/SpA's. If anyone wants to jump on board and help me do this, that would be awesome. I know I could sure use the help! Let's put the nail on the coffin on this one folks!

Best,

Your spunky spondylonian, Jake

Posted By: achala

Re: Potential "Patch" for AS - 11/09/19 07:41 PM

Just to be clear i understnd correctly: you will take Rifaximin that potentially, at least from what I am reading, is used also to treat hepatic encephalopathy and skullcap that potentially can induce liver toxicity as per
https://www.ncbi.nlm.nih.gov/books/NBK548757/#!po=1.38889
And the Rifaximin shall somehow cancel the side effects of skullcap? Will you check for bilirubin, ast, alt, ggt periodically ?

The dendritic cells loss in lymph nodes leading to inflammation of lymph nodes is an interesting theory. Do you have any paper to show connection between gut and various lymph nodes in the neck and occipital area?

Lastly if DCs induce IL-17 expression in HLA-B27 + subjects turning IL-17 over expression with Cosentyx wouldn’t be the most efficient and tolerable way taking into account the below:
https://ankylosingspondylitisnews.c...-years-treatment-ankylosing-spondylitis/
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/09/19 10:38 PM

Originally Posted by achala
Just to be clear i understnd correctly: you will take Rifaximin that potentially, at least from what I am reading, is used also to treat hepatic encephalopathy and skullcap that potentially can induce liver toxicity as per
https://www.ncbi.nlm.nih.gov/books/NBK548757/#!po=1.38889
And the Rifaximin shall somehow cancel the side effects of skullcap? Will you check for bilirubin, ast, alt, ggt periodically ?

The dendritic cells loss in lymph nodes leading to inflammation of lymph nodes is an interesting theory. Do you have any paper to show connection between gut and various lymph nodes in the neck and occipital area?

Lastly if DCs induce IL-17 expression in HLA-B27 + subjects turning IL-17 over expression with Cosentyx wouldn’t be the most efficient and tolerable way taking into account the below:
https://ankylosingspondylitisnews.c...-years-treatment-ankylosing-spondylitis/


You've made a lot of assumptions here. First, the studies showing that skullcap is toxic to the liver are, as you said, merely a possibility. In those cases where people had toxicity in the liver, multiple herbal remedies were being taken simultaneously, so the attribution to skullcap is further weakened. Not only this, the toxicity and damage were reversed completely upon cessation of taking the skullcap. Just as with rifaximin, which should not be taken indefinitely (as mentioned in my first post,) there will be a time when I cycle on and off of these things in my stack. Rifaximin will be cycled somewhere between once every 3-4 months and 6-8 months. Skullcap, around 2-3 months. I have had NO signs of any issues in my current 1-2 months on skullcap. My sleep quality is also notably improved. I am measuring this with my "sleep cycle" app on the iOS store. I used to sleep an average of 4-5 hours a night. I am now sleeping an average of 6.5-7.5. I also feel as if I can fall asleep right around midnight without any fuss.

While rifaximin can treat HE, which is just an infectious agent crossing the blood-brain barrier, this doesn't mean that rifaximin doesn't also treat other infections. I don't see the conflict of using a drug that is purposed for something else, as long as the action of the drug is complementary to the desired outcome. In the rifaximin papers I've submitted before, it has a profound effect of reducing inflammatory cytokines, upregulating PXR gene expression (which is waste and toxin removal) as well as reducing the inflammatory interleukins. It also plays a role in reducing NF-kB signaling induced by LPS coatings.

To be clear, it's not that I WILL use it. I HAVE used it, to much success. Upon cessation, much of my pain returned. I have now procured another non-doctor source (someone else who can get it from their doctor.)

The lymph nodes in the neck/occipital region have both efferents and afferents. Taken directly from Wikipedia:
"The occipital lymph nodes, one to three in number, are located on the back of the head close to the margin of the trapezius and resting on the insertion of the semispinalis capitis. Their afferent vessels drain the occipital region of the scalp, while their efferents pass to the superior deep cervical glands."

Thus there is a link between the cervical region and the occipital region. I, too, get a lot of stiffness and pain in my occipital region, and behind my jaw underneath the ear.

The thing you mentioned about IL-17 is vastly oversimplified. First, the LOSS of DC's primes aberrant immune response and T-cells. It is IL-23 that primes the production of IL-17 producing CD4+ Th17 T-Cells. From Link

"Most of these cell types are activated by IL-23, which can be produced in large amounts by DCs and macrophages exposed to microbial products. Innate T cells such as γδ T and iNKT cells, are particularly potent producers of IL-17 when activated by IL-1 and IL-23 independent of T cell receptor engagement by MHC molecules. Innate IL-17-producing cells are found in the skin, gut mucosal tissues, and lung, and are considered important sentinels for the immune system. They play a role in preserving barrier function through regulation of antimicrobial peptides, and epithelial integrity."

Please scroll down and check out the chart in the above-linked study to see how each different pathway can prime different IL responses.

I'm not sure I understand your argument about Costentyx...it seems a bit oversimplified as each of these interleukins can be induced from MANY sources. It also determines the receptor site density and activity of the later-programmed CD4+ T-cells and others. There is a lot more going on here than a simple "turn off IL-17" switch (which is what Costentyx will do without discriminating how the IL-17 had been triggered.) This is an extremely intricate network. I'm proposing that working on the area of the "gut" being a primary up-regulator of IL-17 activity, due to the lymph and specialized cells there, which do promote IL-17 activity, both directly and indirectly. I DO NOT promote stopping all IL-17 activity, as biologics will do, as this is non-specific behavior. It might reduce your pain, but it WILL lead to more infections and a blunted immune system. To me, this is not the wisest choice, whether it is proving to be "safe" to do or not. It's missing the mark on what the fundamental cause is, as do most drugs sold by pharmaceutical companies.




Posted By: achala

Re: Potential "Patch" for AS - 11/10/19 11:56 AM

Here, in continental Europe Rifaximin is prescribed for Crohne D.

I think what you are describing here is an inflammation of mesenteric lymph nodes where T cell–dependent IgA class switching takes place. However, in case of for example mine (during the first onsets of AAU and AS in general I performed Colonoscopy that indicated Eosinophilic Ileitis), it is more likely thateosinophils contribute to T cell–independent IgA class switching, which mainly occurs in the small intestinal lamina propria, where abundant numbers of eosinophils reside.
Notably the up regulation comes with caloric intake, that would explain the fact that in some instance prolonged fasting can bring benefits, at least for the poeple with similar to mine expressions (but how often we know what really is there, my colonoscopy was purely coincidental)

Eosinophilic link

What activates dendritic cells, and the mechanism could be explained above (interesting article).
Now I am thinking, due to different roots, paths AS was triggered, people fail biologics that answer to specific circumstances... bringing us back to the HLA B27 + predisposition as secondary phenomena in this vicious circle.

just food for thought not a challenge of any kind..., we are all in this wink
Posted By: Caturday

Re: Potential "Patch" for AS - 11/10/19 04:54 PM

Originally Posted by PainintheAS
Ok, everyone...sorry for the extended time period between updates. However, I have been very busy with a new job to pay for all of the expenses I incurred in my downtime from surgery/sickness. A brief update about me, before my updates about everything else:

My coverage for Rifaximin was dropped, as the FDA guidelines allow for 1 initial batch and 2 refills as a limit. I reached that limit and am now fighting with my insurance through grievance/appeals processes (with the help of my GI and his assistant.) I was never 100% free from pain but I was around 80-90% better. My mobility/flexibility was much improved. I could sit in chairs for long periods of time with little-to-no pain. About 1.5-2 weeks after stopping Rifaximin, my pain is significantly worse. I felt it ramping up slowly, and it probably took this long because of the other things I've added to my regimen, which comprise the rest of this message (my update.) So here ya all go.

-------------------------------------------------------------------------------------
The yogurt never came to proper consistency based on multiple trials. I then found a friend with another yogurt maker and did everything as I thought was correct between both yogurt makers at the same time. In conclusion, my yogurt maker is faulty. I have sent in for a replacement. So, updates in the future on that.

Now, here comes quite a lengthy list of things I have been reading about, all very interesting:

1)
Loss of Dendritic Cells (modulate tolerance to "self".) It is the loss of a specific population of dendritic cells that allow tolerance to self-antigens in lymphatic tissue, particularly mesenteric lymph nodes, found throughout the gut that can be attributed to things going "haywire." There's more in this paper about enhanced IL-17 production from the CD4 T-cells, but this is nothing new. I think this paints a clearer picture of how the immune system gets distorted and how important it is to normalize what's going on in the gut.
Link

Further support for how this shaping occurs:
Link

Guess where there is also a large clustering of lymph nodes? You guessed it, right where most of the major regions of pain are for SpA's that relate to the sacroiliac/lumbar regions. Check out this image that demonstrates where the intestinal lymph is drained:
Link

So, the intestinal inflammation comes from the loss of resistance to self, and begins in the gut in the specialized gut lymph nodes. These nodes, then get inflamed, promote aberrant immune cell priming, and then you have both intestinal leakage and an aberrantly tuned immune system. If your gut inflammation is severe enough, then things from the gut will leak into the bloodstream and cause reactions as many studies have already shown (eg. link to Klebsiella, Yersinia, etc.) However, this would also describe why CARBS causes a problem, even in people with no Klebsiella. This is because carbs (as shown in my first post) create immune complexes. If you've lost tolerance for self-antigens due to the loss of dendritic cells, you'll likely react to the carbs that other individuals would have "tolerance" for. In essence, you are attacking pretty much everything because of the loss of dendritic cells. After that, it's just a slow degradation process that erodes and changes the rest of the immune response in many different ways, given your genetics and lifestyle choices.

The other modality of inflammation has already been discussed, which is the upregulation in cytokine/interleukin profiles, which are mediated by the imbalance in the gut (mainly relevant for HLA-B27+ individuals.) For HLA-B27+ individuals, both the above loss of dendritic cells + the change in cytokine expression are going to accelerate the path to the disease state. In those that are NOT HLA-B27+, either an extended period of time with gut imbalance or a breach of the immune system by a foreign invader (periodontal causes mentioned many times,) or a course of damaging drugs (like NSAIDs or antibiotics,) can start this inflammatory cascade...though it would take longer.

This leads me to...

2)
Skullcap (more importantly the compound baicalein found in skullcap) upregulates around 20 different tight junction proteins. Using this in conjunction with rifaximin had AMAZING effects for me. Also, since the gut barrier is very similar to the blood-brain barrier, I referred my friend to start taking skullcap since he has been having issues with a leaky BBB and depressive/anhedonic behaviors. He also perceived incredible results, however, he did get withdrawal symptoms once it wore off (and he gets that with almost everything that modulates either neurotransmitters or inflammation/cytokine profile. His neurological imbalance requires more study on GABA/Glutamate and other cell-signaling mechanics to fully understanding, but it also looks like there is an analog to the loss of dendritic cells in the gut in his case, which would be the loss of astrocytes and microglia for glutamate reuptake after the molecule is first bound to the presynaptic terminal. Interesting parallels!
Link

3)
Turmeric/Curcumin has a variety of effects on various chemical pathways, most notably TNF-alpha activated NF-kB signaling, which is activated by LPS (lipopolysaccharide) coatings of bacteria in the immune system. I've talked about both of these in earlier posts, and TNF-alpha blockers are used to help with AS, so we know this is highly relevant. It also has mood-elevating effects, as well as anti-depressive effects. New generations of curcumin/turmeric supplements are leaving behind the Bioperine-enhanced absorption modality for either nano-emulsion (tween, which is polysorbate-80,) gamma-dextrin (a sugar ring that encapsulates the turmeric and is absorbed in the small intestine,) and lipid-bound delivery methodologies. These new formulations are Meriva, Longvida, Theracurmin, C3/C3-Reduct (which is a high dose of either all 3 of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, or tetrahydrocurcumin (THC) for C3-reduct [I believe],) and a few others. These were the main players for the newer generation of delivery techniques. I have not tried any of these mentioned except for Theracurmin and the gamma-dextrin bound formulations because I believe the other methods of administration have issues related to the heart (lipid-bound molecules can lead to the production of TMAO, which can cause heart issues) or intestinal inflammation (tween [polysorbate 80] delivery method). I decided to try CurQFen and CurcuWin, both having significant short term effects on my pain management while I have been on and off of Rifaximin. These are a great additive to any regimen as they support reducing inflammation to healthy levels. Here is some supporting evidence:
Link
Link
Link

4)
Berberine (found in a few different plants, with berberis aristatis being the most common) is purported to have a variety of positive effects. Mood, blood sugar, lipid, and inflammation seem most notable. It functions similarly to curcumin but with far more wide-reaching effects. There are actually far more beneficial effects, but it seems that similar to turmeric/curcumin, NF-kB signaling is affected, which will downregulate the inflammation caused by LPS coatings from bacteria, as well as a few other modalities of inducing inflammation.
Link
Link

5)
Propionate/Butyrate was mentioned before, but proper ratios are hard to pin down. To respond to the above post, I have tried Tributyrin but felt some pain after using it. Not sure if that was coincidental, however, I have decided that using direct metabolites of bacteria or other processes in the body is often a recipe for disaster. I want to affect the things higher up in the chain so that the production of butyrate is normalized (not normalize it myself.) I think butyrate production is something that should vary with time, based on demand, and the gut microbiome homeostasis is something that dynamically adapts to modulate this. I have tried regular butyrate too and noticed I felt very ill for a short period of time after doing so. Not sure exactly what was going on, however, this is because there is a sweet zone for these metabolites, and too much can impair the gut barrier and proper crypt-depth. I think I may have posted on that before. So, my method of recovery will be related to altering the gut microbiome, increasing tight-junction proteins via rifaximin and skullcap, as well as all of the other benefits rifaximin has to offer (I have procured a non-doctor source until I can get it approved by my insurance again.)
-------------------------------------------------------------------------------------

In my humble opinion, I believe I have found strong enough links that describe each and every step of the process of pathogenesis, including why the specific sites of the spine are attacked, of this disease. I have demonstrated that taking rifaximin has helped me (and others via prior posts,) and that the cessation of its use has caused me to revert to prior symptomologies. I will also provide ANOTHER study that shows that Rifamycin, the parent molecule for Rifaximin, is also better at reducing inflammation AND is reported as SIGNIFICANTLY effective in the management of AS (also in a paper that demonstrates periodontal pathogens can be responsible for AS symptoms.) Here you go:
Link
Link

There's a lot more I've been looking into and a lot more supporting evidence for why tolerance to self is lost but I think that's outside the scope of what I am trying to do here. I probably have another 20 papers you all could read related to FOXP3+ T-cells, and how baicalein can help. I've also found studies that show T-Cells lose memory for what they are normally supposed to do under inflammatory conditions and then become pathogenic, etc.

I've found my stack/regimen that works for me. I am now going to be contacting the man who cured himself in an attempt to spread awareness about this disease and how to treat it. If you read the story of this man, you will find many similar parallels to what's going on here, though his situation was more dire (Castleman Disease.) He's gone on to use a drug that already existed and was prescribed for other conditions in order to treat his own, saving his life in the process. His paying attention to clues that doctors said were irrelevant resembles my own experience quite closely. I'd like to find a way to collaborate with him, and the organization he helped found, the CDCN (Castleman Disease Collaborative Network.) He is also now partnered with the Chan-Zuckerberg "Rare as One" organization, which aims to eradicate diseases. I want to reach out to both David Fajgenbaum and to CZI in order to see if they have ways to help me improve the medical understanding/cohesiveness of various researchers in AS/SpA's. If anyone wants to jump on board and help me do this, that would be awesome. I know I could sure use the help! Let's put the nail on the coffin on this one folks!

Best,

Your spunky spondylonian, Jake



I have posted your thread on reddit. And, let them know you are looking for people to get involved. I would like to help as well if I can. Btw, we both have talked over email this past summer but as you know I had a family member become sick I would like to discuss further with more information that has helped you with this disease.
Posted By: Caturday

Re: Potential "Patch" for AS - 11/10/19 04:57 PM

Originally Posted by achala
Here, in continental Europe Rifaximin is prescribed for Crohne D.

I think what you are describing here is an inflammation of mesenteric lymph nodes where T cell–dependent IgA class switching takes place. However, in case of for example mine (during the first onsets of AAU and AS in general I performed Colonoscopy that indicated Eosinophilic Ileitis), it is more likely thateosinophils contribute to T cell–independent IgA class switching, which mainly occurs in the small intestinal lamina propria, where abundant numbers of eosinophils reside.
Notably the up regulation comes with caloric intake, that would explain the fact that in some instance prolonged fasting can bring benefits, at least for the poeple with similar to mine expressions (but how often we know what really is there, my colonoscopy was purely coincidental)

Eosinophilic link

What activates dendritic cells, and the mechanism could be explained above (interesting article).
Now I am thinking, due to different roots, paths AS was triggered, people fail biologics that answer to specific circumstances... bringing us back to the HLA B27 + predisposition as secondary phenomena in this vicious circle.

just food for thought not a challenge of any kind..., we are all in this wink


Are you a scientist of some kind? laugh
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/11/19 08:31 AM

Originally Posted by achala
Here, in continental Europe Rifaximin is prescribed for Crohne D.

I think what you are describing here is an inflammation of mesenteric lymph nodes where T cell–dependent IgA class switching takes place. However, in case of for example mine (during the first onsets of AAU and AS in general I performed Colonoscopy that indicated Eosinophilic Ileitis), it is more likely thateosinophils contribute to T cell–independent IgA class switching, which mainly occurs in the small intestinal lamina propria, where abundant numbers of eosinophils reside.
Notably the up regulation comes with caloric intake, that would explain the fact that in some instance prolonged fasting can bring benefits, at least for the poeple with similar to mine expressions (but how often we know what really is there, my colonoscopy was purely coincidental)

Eosinophilic link

What activates dendritic cells, and the mechanism could be explained above (interesting article).
Now I am thinking, due to different roots, paths AS was triggered, people fail biologics that answer to specific circumstances... bringing us back to the HLA B27 + predisposition as secondary phenomena in this vicious circle.

just food for thought not a challenge of any kind..., we are all in this wink


While this is interesting, it seems that this theory doesn't fit the bill of IL-23/IL-17 activation. From reading your article, this exists in an IL-5/IL-13 axis. Not to mention, in AS, it is noted that EPC (eosinophilic progenitor cells) are depleted in AS patients (Link.) The drugs that would mitigate the effect you are talking about would be anti-eosinophilic in nature, as mentioned in the conclusion of your article (many drugs similar sounding to that of those that are prescribed for AS, however, they work on different interleukins.) The drug reslizumab is also listed to affect the same interleukin, and is indicated for asthma. I did have asthma growing up, so that is of some interest for me to ponder the lung association.

I think the loss of tolerance to self is causing inflammation that is degrading/depleting specific areas of the intestine of eosinophils, which is why they are found to be depleted in AS patients per the article above. Leaky gut is known to be associated with those that have joint/tendon and soft-tissue disorders. The inflammatory pathways activated by bacteria and other pathogens created by dietary carbs are the kind that can flag the immune system to produce TNF-alpha, which activates NF-kB signaling, which then promotes the IL-23/IL-17 axis. This is the axis described as being both a) correlated with changes in affected individuals through GWAS (genome-wide association studies) and b) the target of the other drugs people are taking (inhibiting their joint/tendon and bone. Rifaximin also works on NF-kB signaling, so the fact that it is beneficial for me and a few others reinforces that it is working on the same pathways as these other drugs, albeit a more targeted inhibition.

I have also been reading on how to stop HLA-B27's propensity to form homodimers, as those are the substances that are binding strange peptides and antigens. The HLA-B27 molecule folds slowly, which is what allows for the creation of homodimers. This activates the UPR (unfolded protein response,) in the cell, which upregulates both NF-kB and, subsequently, cytokine expression (the NF-kB upregulates TNFα, IL-1, IL-6, and IL-23. IL-23 is required for the survival of Th-17 cells.) It has also been shown that certain pathogens take advantage of this pathway, such as Salmonella. That particular pathogen utilizes the UPR to infect cells, and, in HLA-B27+ individuals, the bacterial load to the cell is quadrupled compared to controls! One approach is to reduce the formation of homodimers by using Sulfasalazine. I read into Sulfasalazine and the literature states that it is its IKB kinase inhibitory activity that reduces homodimer formation. These homodimers recognize natural killer cells (KIR3DL2) and these are present on the surface of Th17 cells, which release IL-17 when activated, who have been granted increased survival from the IL-23 via the upregulated UPR. (Link.)

So, I did some more digging on natural IKB kinase (both alpha and beta inhibitors.) Turns out, I was onto something with Baicalein, from skullcap. I mentioned I took it alongside Rifaximin with really great results. Turns out that Baicalein not only stimulates ~20 tight-junction proteins to help seal the leaky intestines, it's also an IKB kinase inhibitor (Link!)

The table provided in this study suggests that there are many natural substances that are IKB kinase inhibitors. Since baicalein is working well for me, I am willing to try a few other of these natural compounds to test their effects. The next goal would be to see how to regain dendritic cells in the intestines and to regain tolerance to self. This would effectively be a double-whammy. You'd reduce the UPR-induced stress as well as reduce the inflammation being upregulated in the intestinal cells.

P.S. I've also found this link between dendritic cells and HLA-B27. It seems that just like in so many of us who have had an "event," and then began to experience symptoms, the dendritic cells are activated after maturation. This starts a transient production of homodimers. These homodimers would then cause the associated binding of peptides and antigens, which then causes more stress. I believe this is why the disease takes time to build because these transient cycles occur over and over until the system is finally degraded enough from the constant barrage of inflammation due to these dendritic cells being activated (Link.)
Posted By: Caturday

Re: Potential "Patch" for AS - 11/11/19 04:23 PM

Originally Posted by PainintheAS
Originally Posted by achala
Here, in continental Europe Rifaximin is prescribed for Crohne D.

I think what you are describing here is an inflammation of mesenteric lymph nodes where T cell–dependent IgA class switching takes place. However, in case of for example mine (during the first onsets of AAU and AS in general I performed Colonoscopy that indicated Eosinophilic Ileitis), it is more likely thateosinophils contribute to T cell–independent IgA class switching, which mainly occurs in the small intestinal lamina propria, where abundant numbers of eosinophils reside.
Notably the up regulation comes with caloric intake, that would explain the fact that in some instance prolonged fasting can bring benefits, at least for the poeple with similar to mine expressions (but how often we know what really is there, my colonoscopy was purely coincidental)

Eosinophilic link

What activates dendritic cells, and the mechanism could be explained above (interesting article).
Now I am thinking, due to different roots, paths AS was triggered, people fail biologics that answer to specific circumstances... bringing us back to the HLA B27 + predisposition as secondary phenomena in this vicious circle.

just food for thought not a challenge of any kind..., we are all in this wink


While this is interesting, it seems that this theory doesn't fit the bill of IL-23/IL-17 activation. From reading your article, this exists in an IL-5/IL-13 axis. Not to mention, in AS, it is noted that EPC (eosinophilic progenitor cells) are depleted in AS patients (Link.) The drugs that would mitigate the effect you are talking about would be anti-eosinophilic in nature, as mentioned in the conclusion of your article (many drugs similar sounding to that of those that are prescribed for AS, however, they work on different interleukins.) The drug reslizumab is also listed to affect the same interleukin, and is indicated for asthma. I did have asthma growing up, so that is of some interest for me to ponder the lung association.

I think the loss of tolerance to self is causing inflammation that is degrading/depleting specific areas of the intestine of eosinophils, which is why they are found to be depleted in AS patients per the article above. Leaky gut is known to be associated with those that have joint/tendon and soft-tissue disorders. The inflammatory pathways activated by bacteria and other pathogens created by dietary carbs are the kind that can flag the immune system to produce TNF-alpha, which activates NF-kB signaling, which then promotes the IL-23/IL-17 axis. This is the axis described as being both a) correlated with changes in affected individuals through GWAS (genome-wide association studies) and b) the target of the other drugs people are taking (inhibiting their joint/tendon and bone. Rifaximin also works on NF-kB signaling, so the fact that it is beneficial for me and a few others reinforces that it is working on the same pathways as these other drugs, albeit a more targeted inhibition.

I have also been reading on how to stop HLA-B27's propensity to form homodimers, as those are the substances that are binding strange peptides and antigens. The HLA-B27 molecule folds slowly, which is what allows for the creation of homodimers. This activates the UPR (unfolded protein response,) in the cell, which upregulates both NF-kB and, subsequently, cytokine expression (the NF-kB upregulates TNFα, IL-1, IL-6, and IL-23. IL-23 is required for the survival of Th-17 cells.) It has also been shown that certain pathogens take advantage of this pathway, such as Salmonella. That particular pathogen utilizes the UPR to infect cells, and, in HLA-B27+ individuals, the bacterial load to the cell is quadrupled compared to controls! One approach is to reduce the formation of homodimers by using Sulfasalazine. I read into Sulfasalazine and the literature states that it is its IKB kinase inhibitory activity that reduces homodimer formation. These homodimers recognize natural killer cells (KIR3DL2) and these are present on the surface of Th17 cells, which release IL-17 when activated, who have been granted increased survival from the IL-23 via the upregulated UPR. (Link.)

So, I did some more digging on natural IKB kinase (both alpha and beta inhibitors.) Turns out, I was onto something with Baicalein, from skullcap. I mentioned I took it alongside Rifaximin with really great results. Turns out that Baicalein not only stimulates ~20 tight-junction proteins to help seal the leaky intestines, it's also an IKB kinase inhibitor (Link!)

The table provided in this study suggests that there are many natural substances that are IKB kinase inhibitors. Since baicalein is working well for me, I am willing to try a few other of these natural compounds to test their effects. The next goal would be to see how to regain dendritic cells in the intestines and to regain tolerance to self. This would effectively be a double-whammy. You'd reduce the UPR-induced stress as well as reduce the inflammation being upregulated in the intestinal cells.

P.S. I've also found this link between dendritic cells and HLA-B27. It seems that just like in so many of us who have had an "event," and then began to experience symptoms, the dendritic cells are activated after maturation. This starts a transient production of homodimers. These homodimers would then cause the associated binding of peptides and antigens, which then causes more stress. I believe this is why the disease takes time to build because these transient cycles occur over and over until the system is finally degraded enough from the constant barrage of inflammation due to these dendritic cells being activated (Link.)


What about with people who are negative for hla-b27 gene? Since, you talk about leaky gut often why not take certain probiotics to help your microbiome go into a less inflammatory state? Have you considered fecal matter transplant or even helminthic therapy? They are running clinical trails for FMTs in denmark and finland for psoriatic arthritis at the moment. The helminths are interesting as they do upregulate IL-10 and other anti-inflammatory properties but I don't know which ones specifically off the top of my head.

So, the article you linked mentioned some chinese herbs that would help assist in IKB kinase inhibitors. And, yet again I can't find a doctor willing to give me Rifaximin sadly.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/11/19 05:42 PM

Originally Posted by Caturday
Originally Posted by PainintheAS
Originally Posted by achala
Here, in continental Europe Rifaximin is prescribed for Crohne D.

I think what you are describing here is an inflammation of mesenteric lymph nodes where T cell–dependent IgA class switching takes place. However, in case of for example mine (during the first onsets of AAU and AS in general I performed Colonoscopy that indicated Eosinophilic Ileitis), it is more likely thateosinophils contribute to T cell–independent IgA class switching, which mainly occurs in the small intestinal lamina propria, where abundant numbers of eosinophils reside.
Notably the up regulation comes with caloric intake, that would explain the fact that in some instance prolonged fasting can bring benefits, at least for the poeple with similar to mine expressions (but how often we know what really is there, my colonoscopy was purely coincidental)

Eosinophilic link

What activates dendritic cells, and the mechanism could be explained above (interesting article).
Now I am thinking, due to different roots, paths AS was triggered, people fail biologics that answer to specific circumstances... bringing us back to the HLA B27 + predisposition as secondary phenomena in this vicious circle.

just food for thought not a challenge of any kind..., we are all in this wink


While this is interesting, it seems that this theory doesn't fit the bill of IL-23/IL-17 activation. From reading your article, this exists in an IL-5/IL-13 axis. Not to mention, in AS, it is noted that EPC (eosinophilic progenitor cells) are depleted in AS patients (Link.) The drugs that would mitigate the effect you are talking about would be anti-eosinophilic in nature, as mentioned in the conclusion of your article (many drugs similar sounding to that of those that are prescribed for AS, however, they work on different interleukins.) The drug reslizumab is also listed to affect the same interleukin, and is indicated for asthma. I did have asthma growing up, so that is of some interest for me to ponder the lung association.

I think the loss of tolerance to self is causing inflammation that is degrading/depleting specific areas of the intestine of eosinophils, which is why they are found to be depleted in AS patients per the article above. Leaky gut is known to be associated with those that have joint/tendon and soft-tissue disorders. The inflammatory pathways activated by bacteria and other pathogens created by dietary carbs are the kind that can flag the immune system to produce TNF-alpha, which activates NF-kB signaling, which then promotes the IL-23/IL-17 axis. This is the axis described as being both a) correlated with changes in affected individuals through GWAS (genome-wide association studies) and b) the target of the other drugs people are taking (inhibiting their joint/tendon and bone. Rifaximin also works on NF-kB signaling, so the fact that it is beneficial for me and a few others reinforces that it is working on the same pathways as these other drugs, albeit a more targeted inhibition.

I have also been reading on how to stop HLA-B27's propensity to form homodimers, as those are the substances that are binding strange peptides and antigens. The HLA-B27 molecule folds slowly, which is what allows for the creation of homodimers. This activates the UPR (unfolded protein response,) in the cell, which upregulates both NF-kB and, subsequently, cytokine expression (the NF-kB upregulates TNFα, IL-1, IL-6, and IL-23. IL-23 is required for the survival of Th-17 cells.) It has also been shown that certain pathogens take advantage of this pathway, such as Salmonella. That particular pathogen utilizes the UPR to infect cells, and, in HLA-B27+ individuals, the bacterial load to the cell is quadrupled compared to controls! One approach is to reduce the formation of homodimers by using Sulfasalazine. I read into Sulfasalazine and the literature states that it is its IKB kinase inhibitory activity that reduces homodimer formation. These homodimers recognize natural killer cells (KIR3DL2) and these are present on the surface of Th17 cells, which release IL-17 when activated, who have been granted increased survival from the IL-23 via the upregulated UPR. (Link.)

So, I did some more digging on natural IKB kinase (both alpha and beta inhibitors.) Turns out, I was onto something with Baicalein, from skullcap. I mentioned I took it alongside Rifaximin with really great results. Turns out that Baicalein not only stimulates ~20 tight-junction proteins to help seal the leaky intestines, it's also an IKB kinase inhibitor (Link!)

The table provided in this study suggests that there are many natural substances that are IKB kinase inhibitors. Since baicalein is working well for me, I am willing to try a few other of these natural compounds to test their effects. The next goal would be to see how to regain dendritic cells in the intestines and to regain tolerance to self. This would effectively be a double-whammy. You'd reduce the UPR-induced stress as well as reduce the inflammation being upregulated in the intestinal cells.

P.S. I've also found this link between dendritic cells and HLA-B27. It seems that just like in so many of us who have had an "event," and then began to experience symptoms, the dendritic cells are activated after maturation. This starts a transient production of homodimers. These homodimers would then cause the associated binding of peptides and antigens, which then causes more stress. I believe this is why the disease takes time to build because these transient cycles occur over and over until the system is finally degraded enough from the constant barrage of inflammation due to these dendritic cells being activated (Link.)


What about with people who are negative for hla-b27 gene? Since, you talk about leaky gut often why not take certain probiotics to help your microbiome go into a less inflammatory state? Have you considered fecal matter transplant or even helminthic therapy? They are running clinical trails for FMTs in denmark and finland for psoriatic arthritis at the moment. The helminths are interesting as they do upregulate IL-10 and other anti-inflammatory properties but I don't know which ones specifically off the top of my head.

So, the article you linked mentioned some chinese herbs that would help assist in IKB kinase inhibitors. And, yet again I can't find a doctor willing to give me Rifaximin sadly.


Yea, I've mentioned HLA-B27 negative people earlier in the thread. I was saying it would be a good idea to go to an immunologist to see what IgA and other immunoglobulins you might be producing. Usually, IgA/IgG to specific pathogens will be elevated. Probiotics are a great idea, but you have to consider if your gut is leaking...you need to be careful what you put in it. The Chinese herbs can help with the sealing of the guts, allowing you to be "safer" when putting probiotics in your system.

For Rifaximin, you'd need to approach it from the "I have IBS" route. Rifaximin is approved for that indication, including SIBO. Look for some studies related to Rifaximin having VERY few side-effects (since it's not absorbed by the body) and also dealing with SIBO/IBS. Present these to a GI, then see if you can get him to prescribe you a trial run (usually 2 weeks.)
Posted By: Caturday

Re: Potential "Patch" for AS - 11/11/19 07:08 PM

So, what would you recommend for hla-b27 negative and positive patients in terms of supplements they can easily acquire to stem the affects of inflammation? What would be your foundation that leads to a protocol? You've done so much research I think you should condense this info and create something like a protocol for people to follow I think this would be easier. I understand everyone is different but this anti-biotic stuff and the research you've shown on this thread has opened my eyes more.

I still think however, ultimately fecal matter transplant is the ultimate way to heal a leaky gut and reverse inflammation permanently in our biome. But, the donors have to be in perfect health and that is hard to find.
Posted By: achala

Re: Potential "Patch" for AS - 11/11/19 07:58 PM

I just checked the several blood counts results i had in the past 3 years and usually my eosinophilic count is at the lower limit end. They put me at that time on Montelukast and Budesonide (Budenofalk), that is glucocorticosteroid to no effect, but I was also on COX-2 inhibitor at that time also to no effect much.

Only after switching to Sulfasalazine for 8 months AAU & Achilles enthesitis subsided. But I cannot use it at this moment due to some other plans so I am back fighting AAU with Predonisone. IKB kinase inhibitor would be a good path to explore.
By the way I understood SSZ doesn't work for Axial but not sure why....
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/11/19 08:25 PM

Originally Posted by achala
I just checked the several blood counts results i had in the past 3 years and usually my eosinophilic count is at the lower limit end. They put me at that time on Montelukast and Budesonide (Budenofalk), that is glucocorticosteroid to no effect, but I was also on COX-2 inhibitor at that time also to no effect much.

Only after switching to Sulfasalazine for 8 months AAU & Achilles enthesitis subsided. But I cannot use it at this moment due to some other plans so I am back fighting AAU with Predonisone. IKB kinase inhibitor would be a good path to explore.
By the way I understood SSZ doesn't work for Axial but not sure why....


If it doesn't work for axial, it could be that my theory is correct and that tolerance to self is lost. You're just attacking the lymph fluids draining from your intestines, which the first place they exit is the lymph network that surrounds the lower spine and sacroiliac region. This would be a different form of attack than say, the homodimers formed by HLA-B27 causing peptides to bind at various sites around the body, including in the eyes.


Originally Posted by Caturday
So, what would you recommend for hla-b27 negative and positive patients in terms of supplements they can easily acquire to stem the affects of inflammation? What would be your foundation that leads to a protocol? You've done so much research I think you should condense this info and create something like a protocol for people to follow I think this would be easier. I understand everyone is different but this anti-biotic stuff and the research you've shown on this thread has opened my eyes more.

I still think however, ultimately fecal matter transplant is the ultimate way to heal a leaky gut and reverse inflammation permanently in our biome. But, the donors have to be in perfect health and that is hard to find.


I was trying to say that going to an immunologist should be your first course, as you need to know what you're reacting to. I don't think fecal matter transplant is the right option for everyone because each person has different genetics and thus will respond to different bacteria differently. We need to normalize the system first, then it will be able to handle the influx of different bacteria more appropriately. If you are not HLA-B27+, then please find out what your body is reacting to by going to an immunologist and checking what IgA and IgG levels are, perhaps do an entire immunoglobulin panel. We cannot say that everyone arrives at the same place via the same route. It is just a common "response" to various assaults on the immune system, which I believe are related to pathogens. I would use EXTREME caution when considering fecal matter transplants...if your immune system is over-reactive, then using even healthy bacteria (but different drastically from what you have currently) then you could be promoting a HUGE influx of new pathogens into your bloodstream, etc. This could then cause even more upregulation of your immune system if done incorrectly or at the wrong time (the immune system is not functioning properly and will misbehave.)
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/12/19 06:44 AM

Also, aside from getting your immunoglobulins tested, the other things I mentioned (turmeric/curcumin and berberine) have anti-inflammatory and antibacterial effects. To me, this would represent a safer first choice than FMT's. If you also want to further reduce inflammation, I agree that specific strains (like the L. reuteri yogurt option) could possibly be good. But I would caution anyone from taking high doses of probiotics in an imbalanced state. Generally, the idea is: clear the bad, then heal the damage (manuka honey is good for this if you can handle the carbs at this point in your disease state,) then restore with beneficial flora. You're opting to throw billions of more organisms into the mix with a potentially leaking gut, then you might be asking for trouble. Take the least risky approaches first and the most gradual changes to allow your immune system time to start down-regulating. More organisms rarely would equal downregulated immune system. The only time I would recommend FMT's is if you have a nasty C.diff infection that has not responded to any kind of antibiotics, etc. Then you need to "crowd it out."

Just my $0.02
Posted By: ck3po

Re: Potential "Patch" for AS - 11/12/19 07:30 PM

Originally Posted by PainintheAS
Also, aside from getting your immunoglobulins tested, the other things I mentioned (turmeric/curcumin and berberine) have anti-inflammatory and antibacterial effects. To me, this would represent a safer first choice than FMT's. If you also want to further reduce inflammation, I agree that specific strains (like the L. reuteri yogurt option) could possibly be good. But I would caution anyone from taking high doses of probiotics in an imbalanced state. Generally, the idea is: clear the bad, then heal the damage (manuka honey is good for this if you can handle the carbs at this point in your disease state,) then restore with beneficial flora. You're opting to throw billions of more organisms into the mix with a potentially leaking gut, then you might be asking for trouble. Take the least risky approaches first and the most gradual changes to allow your immune system time to start down-regulating. More organisms rarely would equal downregulated immune system. The only time I would recommend FMT's is if you have a nasty C.diff infection that has not responded to any kind of antibiotics, etc. Then you need to "crowd it out."

Just my $0.02

Ditto for turmeric, but note that absorption is a challenge. For example, forms that are hydro-soluble will absorb better.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/13/19 02:02 AM

Originally Posted by ck3po
Originally Posted by PainintheAS
Also, aside from getting your immunoglobulins tested, the other things I mentioned (turmeric/curcumin and berberine) have anti-inflammatory and antibacterial effects. To me, this would represent a safer first choice than FMT's. If you also want to further reduce inflammation, I agree that specific strains (like the L. reuteri yogurt option) could possibly be good. But I would caution anyone from taking high doses of probiotics in an imbalanced state. Generally, the idea is: clear the bad, then heal the damage (manuka honey is good for this if you can handle the carbs at this point in your disease state,) then restore with beneficial flora. You're opting to throw billions of more organisms into the mix with a potentially leaking gut, then you might be asking for trouble. Take the least risky approaches first and the most gradual changes to allow your immune system time to start down-regulating. More organisms rarely would equal downregulated immune system. The only time I would recommend FMT's is if you have a nasty C.diff infection that has not responded to any kind of antibiotics, etc. Then you need to "crowd it out."

Just my $0.02

Ditto for turmeric, but note that absorption is a challenge. For example, forms that are hydro-soluble will absorb better.


Yea, definitely an issue with absorption for turmeric. That's why in a previous post (you may not have seen it) I recommended formulations that are in the newer generation of delivery methods. The two I think are the best are CurcuWin and CurQFen, as the others use tween (polysorbate-80, or other lipid molecules that can promote TMAO and cause problems in the heart.) CurQFen is bound to fenugreek fibers, and the other is a gamma-dextrin bound molecule. Both of these formulations are VASTLY improved in absorption over standard curcumin extracts or even those supplemented with Bioperine. There have been many advancements in drug-delivery in the last 10 years, and curcumin is one of the drugs that has benefited from these advancements. Another option is:


Tesseract Tetracumin QR

or

Tesseract Tetracumin SR

These focus on the THC found in curcumin, which is supposed to be one of the strongest metabolites of curcumin. However, my research shows that in some cases it's the THC that will work best on various pathways, while curcumin won't really interact...and others the curcumin has stronger action, while THC doesn't.

Here is the image from a study on curcumin that shows the targets (Link). It is important to note that TNF-alpha, COX, and various other elements in the chain of AS are acted upon, but some by THC more than Curcumin and vice-versa. I'd say it's a good idea to get a good dosage of both of these compounds. I have not tried the THC formulation by Tesseract yet. I have tried CurcuWin, Theracumin, CurQFen, and CurcumRX.

Posted By: PsSpa_M_1989

Re: Potential "Patch" for AS - 11/13/19 05:26 AM

Originally Posted by Caturday
So, what would you recommend for hla-b27 negative and positive patients in terms of supplements they can easily acquire to stem the affects of inflammation? What would be your foundation that leads to a protocol? You've done so much research I think you should condense this info and create something like a protocol for people to follow I think this would be easier. I understand everyone is different but this anti-biotic stuff and the research you've shown on this thread has opened my eyes more.

I still think however, ultimately fecal matter transplant is the ultimate way to heal a leaky gut and reverse inflammation permanently in our biome. But, the donors have to be in perfect health and that is hard to find.


I think your last statement is one of the most curious currently on this forum. In infectious disease clinics, lives have been saved by fecal transplants from newborns to patients hours away from dying, usually due to anti-biotic courses almost obliterating the gut microbiome and thus arresting the function of the immune system.

Hopefully in a not too distant future, we can purchase personalized gut microbiome cultures in the pharmacy, and these ridiculous autoimmune diseases will be a thing of the past (wishful thinking - but here is hoping). Babies are maybe the best donors because their DNA expression is still relatively unspoiled by the stupid high-carb, high-processed diet of contemporary society.

Over and out.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/13/19 08:59 AM

Originally Posted by PsSpa_M_1989
Originally Posted by Caturday
So, what would you recommend for hla-b27 negative and positive patients in terms of supplements they can easily acquire to stem the affects of inflammation? What would be your foundation that leads to a protocol? You've done so much research I think you should condense this info and create something like a protocol for people to follow I think this would be easier. I understand everyone is different but this anti-biotic stuff and the research you've shown on this thread has opened my eyes more.

I still think however, ultimately fecal matter transplant is the ultimate way to heal a leaky gut and reverse inflammation permanently in our biome. But, the donors have to be in perfect health and that is hard to find.


I think your last statement is one of the most curious currently on this forum. In infectious disease clinics, lives have been saved by fecal transplants from newborns to patients hours away from dying, usually due to anti-biotic courses almost obliterating the gut microbiome and thus arresting the function of the immune system.

Hopefully in a not too distant future, we can purchase personalized gut microbiome cultures in the pharmacy, and these ridiculous autoimmune diseases will be a thing of the past (wishful thinking - but here is hoping). Babies are maybe the best donors because their DNA expression is still relatively unspoiled by the stupid high-carb, high-processed diet of contemporary society.

Over and out.


I think FMT's are a good idea for people that don't have bacterially-related issues going on with their immune system; someone who doesn't have a leaky gut at the moment but may currently be experiencing severe imbalance and inflammation. For me, supplementing with probiotics can often bring about increased pain and discomfort if the probiotics are of a type that the LPS coatings are tagged by the immune system as something to attack. This is how HLA-B27 dysregulates the gut microbiome compared to other HLA molecules. For example, Lactobacillus Rhamnosus GG is known to create Polysaccharide A, which allows it to evade detection from the immune system in HLA-B27+ individuals. However, other LPS coatings of bacteria, say Klebsiella, are reacted quite strongly to. This is where being careful about the state of the guts and the state of the immune system, whether HLA-B27+ but not yet in disease state vs. HLA-B27+ and currently in disease state make a HUGE difference on the therapeutic benefit of an FMT.
Posted By: Caturday

Re: Potential "Patch" for AS - 11/13/19 03:38 PM

Originally Posted by PsSpa_M_1989
Originally Posted by Caturday
So, what would you recommend for hla-b27 negative and positive patients in terms of supplements they can easily acquire to stem the affects of inflammation? What would be your foundation that leads to a protocol? You've done so much research I think you should condense this info and create something like a protocol for people to follow I think this would be easier. I understand everyone is different but this anti-biotic stuff and the research you've shown on this thread has opened my eyes more.

I still think however, ultimately fecal matter transplant is the ultimate way to heal a leaky gut and reverse inflammation permanently in our biome. But, the donors have to be in perfect health and that is hard to find.


I think your last statement is one of the most curious currently on this forum. In infectious disease clinics, lives have been saved by fecal transplants from newborns to patients hours away from dying, usually due to anti-biotic courses almost obliterating the gut microbiome and thus arresting the function of the immune system.

Hopefully in a not too distant future, we can purchase personalized gut microbiome cultures in the pharmacy, and these ridiculous autoimmune diseases will be a thing of the past (wishful thinking - but here is hoping). Babies are maybe the best donors because their DNA expression is still relatively unspoiled by the stupid high-carb, high-processed diet of contemporary society.

Over and out.


Do you have any studies that show positive correlation on how babies fmt help people with autoimmune conditions like arthritis specifically?
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/14/19 04:15 PM

Originally Posted by Caturday
Originally Posted by PsSpa_M_1989
Originally Posted by Caturday
So, what would you recommend for hla-b27 negative and positive patients in terms of supplements they can easily acquire to stem the affects of inflammation? What would be your foundation that leads to a protocol? You've done so much research I think you should condense this info and create something like a protocol for people to follow I think this would be easier. I understand everyone is different but this anti-biotic stuff and the research you've shown on this thread has opened my eyes more.

I still think however, ultimately fecal matter transplant is the ultimate way to heal a leaky gut and reverse inflammation permanently in our biome. But, the donors have to be in perfect health and that is hard to find.


I think your last statement is one of the most curious currently on this forum. In infectious disease clinics, lives have been saved by fecal transplants from newborns to patients hours away from dying, usually due to anti-biotic courses almost obliterating the gut microbiome and thus arresting the function of the immune system.

Hopefully in a not too distant future, we can purchase personalized gut microbiome cultures in the pharmacy, and these ridiculous autoimmune diseases will be a thing of the past (wishful thinking - but here is hoping). Babies are maybe the best donors because their DNA expression is still relatively unspoiled by the stupid high-carb, high-processed diet of contemporary society.

Over and out.


Do you have any studies that show positive correlation on how babies fmt help people with autoimmune conditions like arthritis specifically?


A google search shows that clinical trials are being registered for PsA/RA and FMT's. They themselves note in the registration information that they are not sure how to define the proper targets for a "best fit" for each individual. There are also non-bacterial components like bacteriophages, etc. They are uncertain about how to incorporate those elements as well. I know that bacteriophages are used in other countries and have helped with countless conditions in order to fight some pretty powerful bugs. I will note, one person has already died from an FMT because a drug-resistant bacteria that was non-pathogenic in the donor was pathogenic to the recipient and happened to be drug-resistant. Some serious dangers to this option, simply because of differences in the immune system between the two people.
Posted By: Caturday

Re: Potential "Patch" for AS - 11/14/19 08:05 PM

I am already aware of those trails... but trails specifically using baby fmts I am not aware of any such study at this moment. And as for the patient dying to FMTs they didn't screen the donor properly because his gut was bacterial resistant to ecoli. So, they need to screen better but one death out of thousands of FMTs done in the amount of clinical trails done over the past decades... I think FMTs are generally safe but finding the right donor is the real trick that's where it becomes dangerous but someone dying from it is rare.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/14/19 11:29 PM

That's exactly correct and coupled with the fact that I mentioned that these trials indicated they "don't know what to screen for" in PsA/RA patients, this also a large risk to be taking. We are immuno-aberrant individuals. This is not simply combatting a C.diff infection (where most FMT's have been used.) As such, the reactions are likely to be much stronger than those who are simply in a state of acute infection. You mention you want to know how to reduce gut permeability and inflammation. There are MANY other suggestions here that carry far less risk by orders of magnitude that you SHOULD try before you start trying to inject an enormous volume of biological agents into your body. The list of items I've used to drastically reduce my intestinal issues has been mentioned before and they have worked for me by staying consistent. They consist of curcumin/turmeric, berberine, and skullcap (baicalein contained within.) Obviously Rifaximin isn't available to everyone, but it has worked well for me. Sulfasalazine is also an anti-inflammatory that seems to work for many, however, I stay away from it because I try to incorporate natural botanicals whenever possible.

Separately, I am not sure how helpful the infant FMT's will be. An infant's gastrointestinal tract is constantly undergoing RAPID change. One week to another the changes that are taking place are due to the fact that the immune system is currently "learning" how to defend itself from the assaults (bacteria delivered through the mouth by the mother's vaginal fluids, or by skin bacteria in the case of C-section babies, or foods/items being placed in the mouth) You would likely find more consistency in finding a healthy female and sampling the vaginal fluids as that should be relatively consistent in comparison to a baby's hyper-flux.

I would, as a risk-averse approach, try ALL these other naturals before trying an FMT.

Here is a paper stating exactly what I am stating; people with immune-based diseases that have a bacterial element respond far more variably than the successful FMT's for those with C.diff infections.

Link
Posted By: Caturday

Re: Potential "Patch" for AS - 11/15/19 05:50 PM

Originally Posted by PainintheAS
That's exactly correct and coupled with the fact that I mentioned that these trials indicated they "don't know what to screen for" in PsA/RA patients, this also a large risk to be taking. We are immuno-aberrant individuals. This is not simply combatting a C.diff infection (where most FMT's have been used.) As such, the reactions are likely to be much stronger than those who are simply in a state of acute infection. You mention you want to know how to reduce gut permeability and inflammation. There are MANY other suggestions here that carry far less risk by orders of magnitude that you SHOULD try before you start trying to inject an enormous volume of biological agents into your body. The list of items I've used to drastically reduce my intestinal issues has been mentioned before and they have worked for me by staying consistent. They consist of curcumin/turmeric, berberine, and skullcap (baicalein contained within.) Obviously Rifaximin isn't available to everyone, but it has worked well for me. Sulfasalazine is also an anti-inflammatory that seems to work for many, however, I stay away from it because I try to incorporate natural botanicals whenever possible.

Separately, I am not sure how helpful the infant FMT's will be. An infant's gastrointestinal tract is constantly undergoing RAPID change. One week to another the changes that are taking place are due to the fact that the immune system is currently "learning" how to defend itself from the assaults (bacteria delivered through the mouth by the mother's vaginal fluids, or by skin bacteria in the case of C-section babies, or foods/items being placed in the mouth) You would likely find more consistency in finding a healthy female and sampling the vaginal fluids as that should be relatively consistent in comparison to a baby's hyper-flux.

I would, as a risk-averse approach, try ALL these other naturals before trying an FMT.

Here is a paper stating exactly what I am stating; people with immune-based diseases that have a bacterial element respond far more variably than the successful FMT's for those with C.diff infections.

Link


Yeah, it's always a big risk. I hope they can figure this stuff out in the near future. Look into r/humanmicrobiome this whole sub reddit is focused driven on gut health news, scientific research, and FMTs I think you'll find some interesting information on there.
Posted By: PainintheAS

Re: Potential "Patch" for AS - 11/26/19 09:05 PM

Also, returning to a prior bit of discussion as to whether biologic treatment was responsible for an increased rate of cancer or not...I have found this study which indicates that HLA-B27 is protective against certain forms of cancer:

https://www.cancertherapyadvisor.co...7-positivity-did-not-influence-outcomes/

So, just reiterating then that since there HAS been evidence (whether or not it's solidly proven yet) that biologics can have an increase in cancer rate, whereas HLA-B27 is now found to be protective against these cancers...I will stand by my decision not to take biologics and continue to try and find therapies (other than the ones that are currently keeping my symptoms in check) in order to both a) improve my quality of life and b) move forward the progress for others to come and hope to save people from pain in a way that doesn't increase their risk of infections or, possibly, cancer.
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