Preventing Autoimmune Disease: How Healing the Gut Can Help 06/20/2019 (originally published 07/12/2010) – Autoimmune diseases taken together are the third leading cause of death in the US.  The list of autoimmune diseases is long and varied—M.S., type 1 diabetes, lupus, Hashimoto’s thyroiditis, rheumatoid arthritis, Sjogren’s, and fibromyalgia to name just a few.  But the autoimmune disease celiac, unlike all the others, has a unique feature—it’s the only autoimmune disease where the exact trigger is known.  Gluten is the trigger for celiac disease and when that trigger is removed the body stops destroying its own small intestine.

Why is this profound?  Two reasons:

  1. There is no other autoimmune disease where the exact trigger is known.
  2. Gluten and the damage it causes to the small intestine may very well be the root cause of other autoimmune diseases!

We have appreciated the interesting phenomenon where people “develop” gluten intolerance at different ages.  It used to be perplexing because it was assumed that if the problem was genetically driven, as soon as the body received its first gluten “insult” damage should begin to occur.  When patients stated that they felt perfectly fine until a certain age, it was thought that the damage had probably begun far earlier but the patient had just not noticed.  What we have come to realize is that a genetic propensity plus the presence of gluten in the diet are only two of the three necessary constituents of the puzzle—the third is damage to the small intestine.

A completely healthy, intact small intestine seems to be quite able to defend itself against gluten.  But once damage has occurred, the gut becomes “leaky” and not only can digestive complaints result but symptoms arise in other body systems.  There has been proof for many years that the intestine is not the only tissue targeted by the immune reaction to gluten.  The prime example of this is a disease called dermatitis herpetiformis where the gluten sensitivity manifests primarily in skin, with only mild or no intestinal involvement.  Now, more recent research reveals that perhaps a vast number of autoimmune diseases may also involve an immune response to dietary gluten as well as its consequent autoimmune reaction to tissue transglutaminase.  This may be the main immunologic cause.  [Note: Although we typically think of tissue transglutaminase as an enzyme in the gut, it is, in fact, an enzyme found throughout the body.  This is perhaps another reason why gluten has such far-reaching effects in other systems of the body.]

The substance that dictates the permeability between the barrier cells that line the small intestine is called zonulin.  Increased zonulin causes the intestine to become leaky, thereby allowing substances to leave the intestine that normally shouldn’t.

Research has shown that in patients with celiac disease, gliadin activates zonulin signaling, leading to increased intestinal permeability.  But how does this extend to other autoimmune diseases?

Dr. Alessio Fasano performed a brilliant study on rats that were genetically predisposed to develop type 1 diabetes.  The premise was that if the gut was not affected negatively by zonulin and remained intact and healthy, then perhaps the auto-antibodies made against specific cells of the pancreas that create diabetes would be prevented from leaving the gut and thereby stopped from causing damage to the pancreas.  Sure enough 2/3 of these rats who were highly predisposed to develop diabetes did not!

This study was the first time that an autoimmune disease was prevented by blocking intestinal permeability.  It further puts a new face on the entire concept of how and why autoimmune disease develops.  We’ve always thought that the genetic predisposition was an overriding characteristic of autoimmune diseases that overshadowed any effort to sublimate it.

This study opens a new field of investigation into the relationship between the health of the intestine and the basis of many diseases.  Imagine if the “unknown trigger” of autoimmune disease turns out to be gluten and its effect of creating a leaky gut!

It is for this reason that I am so passionate about early diagnosis of gluten intolerance.  Whether it be celiac disease or gluten sensitivity, the effect that gluten imposes on the integrity of the small intestine has far-reaching implications.  I see it clinically in my patients on a daily basis, but the above research puts a point on it that we must consider seriously.  

A study from Italy showed that the longer gluten sensitive people eat gluten, the more likely they are to develop autoimmune diseases.  They found that in childhood celiacs, the prevalence of autoimmune disease rose from a baseline of 5% at age 2 to almost 35% by age 20.  Imagine if screening of all children for gluten intolerance resulted in reductions of future autoimmune diseases!

I am currently working on a program with my patients who are gluten intolerant to restore their small intestines to the healthiest possible condition.  This is important from the obvious viewpoint that optimal digestion and absorption is critical to good health.  But it is also vital from the perspective of understanding and managing zonulin and its long-term effects on health.

I would recommend that you take the following steps to ensure that you are doing everything you can to restore your small intestine to optimal functioning.

Have a comprehensive stool analysis performed to ensure that no pathogenic organisms (bacteria, amoeba, parasites, etc) are present.  Such a test should also measure the effect of your body’s enzymes to see how effectively your food is being broken down and absorbed.  It should also assess the health of your intestinal bacteria or probiotics.  

Eliminate dairy foods from your diet.  There is considerable evidence to suggest that consuming milk from other mammals is not conducive to good health, especially in our digestive tracts.  The inflammation that dairy can cause could well be contributing to a leaky gut, despite the elimination of gluten.

Once you have taken the above steps, see how you’re feeling.  Some patients require supplements such as glutamine, quercitin, reduced glutathione, N-acetylcysteine, omega 3 fatty acids, and vitamins A, E, B and zinc to help the intestinal lining heal fully.  

Once the above have been done, have a lab test performed for leaky gut.  It’s called a lactulose/mannitol test and will show whether large molecules are crossing the intestinal barrier.  This is a non-invasive, non-drug test.

Just to reiterate: encourage parents you know to have their children evaluated for gluten intolerance.  The more we can affect an early diagnosis, the healthier our future generations will be.

Last but not least, show your doctor this data.  There is still too much ignorance in our profession about gluten and its broad reaching negative effects.

I hope you find this information helpful.  Many of the steps mentioned above are best administered with the help of a clinician so let me know if I can assist you to find someone in your area who can help.  


  • Scandinavian Journal of Gastroenterology. 2006 Apr;41(4):408-19.
  • Annals N Y Academy Science. 2009 May;1165:195-205.  “Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms.”
  • Clinical Gastroenterology & Hepatology. 2005 Apr;3(4):335-41.  “Permeability, zonulin production, and enteropathy in dermatitis herpetiformis.”
  • Gut. 2003 Feb;52(2):218-23.  “Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.”

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