Leaky Gut and Autoimmune Disease (Ankylosing Spondylitis)
The Leaky Gut Hypothesis and Pathogenesis of Autoimmune Disease
This is going to be a very long post about my Ankylosing Spondylitis history, what I’ve tried, what I’ve been through, and why I believe leaky gut is the key to nearly all autoimmune disease and chronic inflammation. I will put a quick TL;DR up front and then a small novel to follow. If you want to skip my history and framing of science, you can jump down to “OK SO WHAT IS LEAKY GUT”
TL;DR
Ankylosing Spondylitis is considered to be an inflammatory disease / autoimmune disease where your immune system is attacking your spine. As parts of the spine are chronically inflamed, the body’s response is to slowly fuse the bones together until all mobility is lost and the spine bamboos into a single bone.
My current status is my AS is in remission through cutting out gluten and stress. All my pain symptoms are gone and inflammation markers are down to baseline. I’m weaning off of Humira now (and have been weaning off of it for the past 12 months). As of now I am at one injection every 8 weeks.
I do believe in the leaky gut connection with autoimmune disease. I do not believe there is a one size fits all fix for this. I do believe the science is so early stage in this field that the best we can do is self-experiment. I say “believe” because again, there is not a lot of hard science in the field of auto immune disease and leaky gut. There is so much we do not know.
QUICK BODY STATS
As of this writing (December 2018), I am 33 years old. 6 feet tall and currently about 205lbs. I bulk and cut between 170-200~ lbs or so. (This is a side hobby to build some muscle and burn some fat. This has nothing to do with AS). My AS symptoms are in remission and I’m in the best shape of my life right now. I’ve thankfully only had some permanent damage to my right si joint. Besides that my back issues are all under control now.
HEALTH HISTORY
Even though I probably had AS since my early or mid 20’s, I was not diagnosed until 31. It was misdiagnosed through different doctors for years until I found my way to my rheumatologist and suggested to her I might have AS where she confirmed it. I went on humira around this time. After 2-3 months of being on humira my mid back pain that caused sleepless nights went away magically and I was finally able to sleep.
I’ve always treated humira as a wonder drug that is just buying me time until I figure out why I have autoimmune disease. I was not convinced by the typical doctor’s belief that it is just a random genetic lottery issue. I believe environmental factors could control it and I was determined to experiment.
I was never really resilient as a kid. I was born through C-section and was always a super “clean” kid. Never really got that dirty. Always kind of sick and having allergies growing up. I was never really strong. My dad has psoriasis and my mother has lupus. My brother so far has nothing going on.
I’ve had 6 different major back issues in my life. Pretty much all of them are under control now. Let’s go through each of them.
1) MID BACK PAIN FROM SLEEPING
My AS symptoms started around my 24th birthday. I was going through the most stressful breakup of my life and waking up daily with that ball of stress in my stomach. After a few weeks of this massive stress, that’s when my first major AS symptoms started. I could not sleep more than 5-6 hours without waking up with mid back pain. That mid back pain was around my T8-T12 region and would only subside after getting up, moving around for 30-60 minutes, and then I could go back to sleep. Otherwise my choice was to sleep at a steep incline which was already hard on my low back.
STATUS: In remission. I believe it was due to fixing the leaky gut problem, but I will get into that in more detail later. Taking humira initially cleared this pain within 2-3 months.
2 AND 3) SI JOINT DEGENERATION + PIRIFORMIS SYNDROME
Piriformis syndrome is very similar to sciatica. When these two issues flare up, I can barely walk. I have crushing pain in my butt cheek and have to crawl or use a cane. It’s possible my AS symptoms also started when I was around 22 with this pain. My right SI joint had some crushing pain that caused great pain on my sciatic nerve. After seeing several specialists, it seems that it was a combination of my SI joint having degeneration triggering piriformis syndrome all of which COULD have been started by my AS. Won’t ever know for sure, but those 3 issues did exist. Thankfully I do not have issues walking anymore.
STATUS: SI joint still has permanent damage, but it has stopped getting worse. I have lost the ability to do certain strength movements that involve hip opening or single leg exercises. E.g., if I do lunges, wide stance squats, or hip opening stretches, I am playing with fire and risking a relapse of my piriformis syndrome. As long as I know my limitations and do some glute stretches, it seems to stay under control.
STRETCHES: I did figure-4 glute stretches and knee to chest stretches. With the knee to chest stretches, it was critical for me to pull the knee to the opposite breast to get a nice deep stretch in my glutes. I had to be careful to not overdo these as it could make it worse.
4) TYPICAL LOW BACK PAIN
This was just the typical generic low back pain that most people suffer from. I do not think this was AS induced at all. I think this was purely a postural problem. I had L4-L5-S1 bulging disks with a 3-4mm bulge. I had dull numbing pain in my low back and toes.
STATUS: Pretty much 100% gone. I have occasional days where I do something stupid with weight lifting or have bad posture on the couch and I can feel it creep back up. It will go down within a few days as long as I am more mindful of it.
FIXES: Learning proper posture of the lumbar and keeping the neutral curve while sitting, standing, etc. was immensely helpful. Some yoga stretches helped as well (cobra, bridge, and cat-cow). Deadlifting WITH GOOD FORM was also very helpful. Deadlifts done correctly will teach good posture (how to sit the hips back) and strengthen your back.
5 AND 6) UPPER BACK PAINS
These are barely worth mentioning because I do not think others will have similar issues. These were rare circumstantial problems that are fixed now, but I will talk about it briefly. It is unlikely these were from Ankylosing Spondylitis at all.
NOT CHEWING FOOD – Around 20 years old, I was waking up with random pain along the left spinal erector muscle around T4-T8 regions. This was also when I happened to get braces for the first time and I was barely chewing my food and swallowing. I had no idea what the issue was, but I mentioned it casually to my Korean friend. My Korean friend then asked her grandma (who was a chiro and eastern medicine doctor) who immediately told her to tell me, “you need to chew your food.” No idea how she was able to make that connection so fast on such limited information. Sure enough, I chewed my food thoroughly from there on out and within a few days the pain never came back.
STUPID SELF INJURY – During my desperation to get sleep, in my late 20’s I was convinced my mid back just needed to be adjusted to “bend the bones back into place”. I was ignorant and desperate. I was holding onto a post and trying to bend my spine into some forceful flexion positions. I created a translational injury around the T3-T4 (sharp pain between shoulder blades) that a chiro has since fixed my stupidity. Occasionally it comes back when my posture is poor and my arms are too far forward from my body at my desk.
Now on to leaky gut.
WHY IS LEAKY GUT A TOUCHY SUBJECT?
For some reason, this is a touchy subject. I think many of us are jaded from all the snake oil BS we have been sold when it comes to remedies and fad diets. It is all too common that a BS “doctor” TV personality hears the latest craze and then passes it on as gospel to all of us. We spend lots of money on failed fixes only to become more jaded.
As always with the media, it seems all too easy to become polarized in what we hear. When it comes to gluten and the “evidence based” crowd, it’s become polarized. One camp says gluten free will cure everything and turn you into an immortal. The other group screams at you for daring to consider going GF if you’re not a celiac.
(Note: I consider myself evidence based and I said “evidence based” in quotes because a small group of the “evidence based” folks have really strong biases in favor of a small percentage of scientific evidence casting doubt on non celiac gluten issues, but ignoring the growing body of evidence for non celiac gluten issues. Their biases are driven by disdain for fad diets and are quick to group any diet as a fad diet)
As always, the reasonable truth is somewhere in the middle. I will do my best to explain what is a hard scientific fact and what is theory and hypothesis.
WHAT ARE THE LEVELS OF EVIDENCE?
When it comes to science, there are different levels of evidence. You might hear some people say, “There is no conclusive evidence that leaky gut causes autoimmune disease.” This very strongly worded statement could actually have 3 different meanings:
- 1) Very little to no science has been done on the subject, therefore there is no conclusive evidence.
- 2) There is some evidence for it and some against it, but more studies need to be done to prove it one way or the other.
- 3) The evidence conclusively shows the opposite is true (E.g., eating lots of gluten helps prevent autoimmune disease is the opposite conclusion of what is hypothesized).
As of now, most of the science for leaky gut and autoimmune disease falls into the first category, but the evidence is growing stronger that there is indeed a link. It’s correlation. It is not a proven casual mechanism yet.
It is rare we discover a causal mechanism. The typical flow of science goes something like this:
Anecdotal stories –> Observational and correlational studies –> Animal trials –> Poorly done human trials –> Well done human trials (Randomized double blinded placebo controlled) –> Mechanistic action discovered
That oversimplified chain of events could take decades and millions of dollars to fund the studies to get the quality science done. Even after the mechanism is discovered and agreed upon in the scientific community, it can still take decades for the medical schools and books to be updated to teach the newer generation of doctors.
Often the older generation of doctors are too busy to stay updated on the latest research. They’re busy with managing their practice, trying to pay off debt, dealing with insurance, and helping patients who don’t care about their health. We are creatures of habit and I do not blame doctors for not staying updated on the research.
WHY ISN’T THERE MORE FUNDING FOR STUDIES ON ANKYLOSING SPONDYLITIS?
Money makes the world go round. The unfortunate truth is AS is not that common and treating any disease through lifestyle change is not an investment companies can see a return on. I’m not anti-pharma or conspiracy theory about this stuff. The fact of the matter is drug companies are able to produce a ROI through drug based solutions and a lot of research will get funded this way favoring drugs over lifestyle changes. This research will always move faster compared to research regarding dietary changes.
OK SO WHAT IS LEAKY GUT?
There was a major mechanism discovered in the 90’s by Dr. Alessio Fasano. He accidentally discovered a new hormone in our intestines called zonulin. Zonulin is a hormone that regulates the barrier junction tightness between our intestinal wall. Our intestinal wall tightness should be very tight. The intestinal wall is only one cell layer thick (it’s a very thin wall). When zonulin is upregulated, the spacing between the intestinal walls increases. Zonulin is a hard science. It’s not debatable. Yet, many doctors have never heard of it depending on when they were trained or if they stay up to date on the research.
It was also discovered that gluten will upregulate zonulin production in everyone (celiacs, non-celiac gluten sensitive individuals, and normal people). This is hard science.
Note that zonulin is not the only hormone responsible for gut permeability (e.g., TNF, IL-13 are some others). There is much we are still learning, and the science will continue to evolve over the coming decades.
This is where the hard science stops and now the hypothesis comes in. There is some evidence for this hypothesis, but we are probably still decades away from getting a solid scientific conclusion.
LEAKY GUT – Leaky gut (AKA intestinal permeability AKA GAPS) is the condition where the intestinal junctions are letting undigested food particles or pathogens slip into the bloodstream. This could be small bits of carbs or proteins or it could be pieces of bacteria or entire cells.
Through a mechanism called molecular mimicry, certain foreign bodies will share some resemblance to something in our body, which can lead to the immune system attacking both the foreign particle and the part of our body that looks like it. For example, one often quoted molecular mimicry for Ankylosing Spondylitis is how parts of our spine share similarities in protein structures to a bacteria called Klebsiella Pneumoniae. Dr. Ebringer is a leader in this hypothesis that the pathogenesis of AS is from this particular bacteria. This is a theory and I won’t go into a lot more detail here about it, but you can google for more details.
HOW DOES LEAKY GUT CAUSE AUTO IMMUNE DISEASE?
The hypothesis goes something like this. There are 3-4 components that are required to kick off an autoimmune disease.
- 1) Leaky gut – You have a leaky gut and some things are slipping through into the bloodstream that should not be there. Leaky gut is usually induced by something you’re eating (or stress).
- 2) Diet – Something in your diet is slipping through into your bloodstream or causing the gut microbiome to shift and certain food/pathogens are slipping into the bloodstream.
- 3) Genetics – You are genetically predisposed to whatever is slipping into the bloodstream to have your immune system flare up and try to attack it and then your body through molecular mimicry.
- 4) Stress – When I say stress, I mean a stressful traumatic event (E.g., mental stress from family drama, a car accident, a serious bacterial illness, etc.). Although not always necessary, it seems to be a common catalyst in autoimmune disease. Perhaps it kicks off the immune response into a positive feedback loop. Perhaps it induces a greater degree of leaky gut, but we’re not sure.
HOW DO YOU FIX LEAKY GUT?
This is where we get into the your miles may vary. No matter whatever solution you try, most people should see some kind of results after 2-3 months of a serious effort. If you aren’t seeing any noticeable changes after 2-3 months, consider changing treatment methods. After researching and reading through the different methods. From what I can tell, these methods seem to be the most practical and cheapest ways to try and fix a leaky gut.
1) Gluten free
Gluten is the lowest hanging fruit to knock off first. Again, it is a hard science that gluten upregulates zonulin production. Non celiac gluten sensitivity is widely recognized in the scientific community with about 700 studies referencing it in Pub Med.
By cutting out only gluten, it is possible you can fix your leaky gut and symptoms could subside over time.
2) Keto diet
I will not dive into the keto diet and the “fat burning” properties people use it for (spoiler alert, it’s not a magic fat loss diet). Besides having some proposed general anti inflammation properties, a keto diet can help in fixing the leaky gut through a few other proposed mechanisms. Gluten and similar proteins to gluten can be found in other starchy grains (rice, corn, etc.). It’s possible some people have cross reactive sensitivity to those gluten-like proteins. Therefore, cutting out all starch could help.
The Klebsiella Pneumoniae hypothesis also synergizes with the keto diet because that bacteria largely feeds off starch. The theory goes that if you starve the bacteria of starch, it will go back down to normal levels and AS symptoms will go into remission.
3) AIP (Auto immune protocol) diet / Elimination diet
AIP is an extreme version of paleo that essentially cuts out ALL potential gut inflaming foods (gluten, coffee, sugar, dairy, tomatoes, FODMAPs, etc.). You’re basically left with a few vegetables and meats. You go on this diet for 2-3 months and then start to reintroduce foods one at a time and see what triggers your symptoms. AIP is not meant to be a lifelong diet.
It is my opinion that the AIP diet is the ultimate elimination diet as the most comprehensive shotgun approach. Whole30 is an example of another elimination diet that starts with eliminating a some things, but is not as comprehensive as the AIP diet. I think the widest shotgun approach makes the most sense because elimination diets are very inconvenient to go through. However, the choice is up to you.
Bonus tip: you’re likely to lose weight on an AIP diet since you cut out so much food that you will likely be forced to eat less calories daily on this particular diet.
WHAT ABOUT SUPPLEMENTS?
I’ve dabbled in different supplements and from what I’ve learned, it seems the two main supplements worth considering are:
GLUTAMINE
This is just a simple amino acid (part of a protein). It is a hard science that glutamine can improve general gut health. Glutamine is used for a lot of gut repair and is safe to take in large doses.
You can find glutamine powder for about $15-20/lb or sometimes on sale for about $8-10/lb. 0.5-1 pound will probably work for most people to try for a month or two. Glutamine powder is the most economical. It doesn’t matter where you get it from. Most protocols call for 10-20g of glutamine daily consumed however you want. It’s actually kind of sweet and I mix it with water or juice.
BONE BROTH
Bone broth is somewhat tasty and easy to make at home. Bone broth is basically amino acid (protein) soup. I have not personally taken bone broth for my leaky gut, but I know it can be helpful for the leaky gut with collagen, glutamine, and proline found in bone broth.
Making your own bone broth at home is the cheapest way to go. You can look up protocols online, but basically use a slow cooker or pressure cooker with any bones you have on hand. Cook for 12-24 hours in the slow cooker or 2-3 hours in the pressure cooker. Enjoy the broth. Some protocols also call for intermittent fasting + bone broth to give the gut a break and a chance to heal.
MY LEAKY GUT PROTOCOL
I went gluten free and consumed about 15-20g of glutamine daily for a month. After 3-4 months of gluten free, I started skipping humira injections and I had no symptoms return.
I wanted to change as little as I could about my lifestyle and hopefully see results. For that reason, I decided to just try gluten free first and then consider possibly doing a keto or AIP diet.
After being gluten free I decided to try skipping my humira injections. Previously when I would miss humira injections, I could go 3 weeks of missing my injections before my symptoms of mid back pain while sleeping would slowly creep back in.
After being gluten free, I was able to go 12+ weeks without my injection and still no pain returning. I did a test and ate a lot of gluten in a day (donuts, burritos, beer, etc.) and my symptoms started to return 2-3 days later. I also did a second test along similar lines with similar results.
While writing this very long article, I decided to test a third time with gluten to be sure. I consumed a gluttonous amount of gluten one day. It was a challenge. In one day I consumed 3 pastries, 1/4 of a birthday cake, 2 meals of noodles, and half a doughnut. Everything else in my diet that day was the same. My levels of stress prior and during that day were baseline normal. The next morning I woke up with a stiff mid back after 6 hours of sleeping. A stiff back feeling I hadn’t felt in months.
I want to point out that my experience is an anecdote and one of many anecdotes that have had similar results. I also want to point out that again, this is not a confirmed causal mechanism and I’m a study of one person. It will take decades before we can safely say there is a causal mechanism here. However, I am able to reduce the dependency on my drug significantly through this dietary change.
As of this writing, my schedule for humira injections is around once every 8 weeks and still weaning down. I’d like to cold turkey it, but my rheumatologist wants to play it safe with a very slow weaning off the drug. In fact, my rheumatologist does not want me to ever reduce below once every 8 weeks for Humira. I’ll likely monitor my condition over the next 2-6 years through X-rays and pain levels. If the disease does not progress I will consider going off of it entirely.
I can also consume some gluten in moderation without having symptoms return. Since I am not celiac, the dose makes the poison. Gluten is a wheat protein. The amount of wheat protein found in pasta or a pastry will be much higher than the amount of wheat protein found in beer or soy sauce.
Here are a few examples. I’ll treat myself to a doughnut once a week and I do not have symptoms return. I still drink a beer here or there and do not worry about using soy sauce with my food. If I’m eating out with friends or family, I will still nibble on some wheat based dishes, but no more than a few bites typically.
HOW DO I GET TESTED FOR LEAKY GUT?
There are no good tests for leaky gut. This is really cutting edge science where there is still a ton we do not know. A lot of tests are unreliable and expensive. Chances are, if your insurance covers the test, then it’s an unreliable test. If the test requires all cash (e.g., Cyrex Array tests), it’ll be more comprehensive, but costs hundreds of dollars cash. The most practical test is to simply self-experiment with changes and see if it makes a noticeable difference. The key there is noticeable. If it’s not noticeable after a few months, move on and try something else.
GENERAL TIPS:
- Pay attention to your gut health and poops. If your poops do not look normal (google for bristol stool scale to see cartoon examples), then seriously consider tweaking your diet until it looks normal and you discover your triggers. My triggers include nightshades (tomato-based dishes like tomato soup or chili), too much coffee, stress, and more.
- FODMAPs is something I did not deep dive, but it is worth a quick mention. FODMAPs are basically the “healthy” carbs (fruits and veggies) we typically think about in health media. We would never think apples, onions, or beans would be bad for us, but those foods are just a few FODMAPs and could actually be harsh on our guts. If it causes problems for our guts, then it could cause seemingly unrelated health problems downstream. There are dozens of FODMAPs out there and FODMAP sensitivity is very individualized. If you’re experimenting with eliminating foods from your diet, consider looking at the list of FODMAPs.
- Try something out for 2-3 months. If it’s not working for you, move on.
- Ignore any health media or resource that paints a black and white picture. If someone is claiming something to be a panacea cure all (e.g., bone broth), it’s not. Do not listen to that resource any longer. Fear mongers and snake oil salesmen usually say something like, “THIS ONE THING THAT EVERYONE IS DOING IS SECRETLY KILLING THEM”.
- Although I state gluten (something everyone eats) is upregulating zonulin, I try to give proper context and point out how the individual response will vary. This is a reasonable explanation. I try to avoid sites that state “WHY GLUTEN IS SECRETLY KILLING YOUR HEALTH AND BIG WHEAT DOESN’T WANT YOU TO KNOW”
- All that said, I do suspect that there are many people out there who can safely consume gluten their entire lives and never develop chronic inflammation or auto immune disease. At the same time, I do think there is a high proportion of people who cannot handle gluten as well.
RESOURCES AND STUDIES
I’m also a Twitch streamer and run a Discord for content creators with chronic inflammation or autoimmune disease. If you are a content creator (or know someone who is a content creator), let me know and I can send you an invite! ?
AIP diet — https://ultimatepaleoguide.com/autoimmune-protocol/
Dr. Mark Ruscio — Functional medicine doctor focused on gut health. He is reasonable and looks at the evidence.
Phoenix Helix — Podcast for auto immune disease.
Power Health Talk — Podcast hosted by two functional medicine doctors mostly focused on auto immune health.
FX Medicine — Functional medicine doctor podcast.
Dr. Alessio Fasano — Leading doctor and scientist who discovered zonulin and researches leaky gut. He has many resources out there, but an easy one is find his podcasts where he’s a guest.
Dr. Ebringer — Scientist who started the research about the connection between gut bacteria (klebsiella pneumoniae) and Ankylosing Spondylitis.
There are many many articles on Pub Med acknowledging the theory and possibility of leaky gut and autoimmune disease. Here are a few:
Example of leaky gut and autoimmune disease hypothesis
Gluten increases intestinal permeability in all individuals (including normal healthy people)