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 CausesStandard/Common Klebsiella TheoryLink 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!