Leaky Gut: Connection with Autoimmune Diseases

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Is leaky gut a prerequisite to developing an autoimmune condition? Dr. Alessio Fasano thinks so.

Autoimmune diseases have been an interest of mine since learning that a close friend had been diagnosed with multiple sclerosis at a young age. Before that point I had never looked deeply into what an autoimmune condition actually was. Not unlike conventional medicine I began my study on individual autoimmune conditions, learning their pathologies and unique features that set them apart. It wasn’t until I came across Chris Kresser’s work that I made the connection (thanks to his writing) that all autoimmune diseases share common ground in immune system dysregulation. Many of his writings link to the research that Alessio Fasano has done to bring this point home.

This article will cover one specific aspect and possibly a prerequisite to developing an autoimmune condition that Dr. Fasano has been writing on for years. Intestinal permeability, aka leaky gut. More on what leaky gut is here.

In a paper entitled Leaky Gut and Autoimmune Diseases Fasano lists a few current or ‘classical’ theories on the development of autoimmune diseases.

Classical Theories- The Development of Autoimmunity

#1. Molecular Mimicry aka Viral and Bacterial infections – ‘The connection between infection and autoimmune disease is often explained by a mechanism known as “molecular mimicry,” whereby microbial antigens are postulated to resemble self-antigens. The induction of an immune response to the microbial antigens results in a cross-reaction with the self-antigens and the induction of autoimmunity.’

This theory postulates that the immune response will continue in the cross-reaction attack even when the infection, or ‘environmental trigger’, has been removed.

The paper references animal studies that show this process in effect. It goes onto reference the same paper were human studies have shown molecular mimicry to be a process that pushes a pre-existing autoimmune condition forward.

#2. The Bystander effect – The bystander effect is another classical theory on the development of autoimmune conditions. It proposes a similar idea to molecular mimicry in that it involves a microorganism (viral, bacterial, fungal etc) The difference in this theory is that the infection damages one’s body tissues, exposing the immune system to self-antigens.

Pre-existing Conditions for Autoimmunity

The paper lists three conditions that lead to the development of an autoimmune process.

  1. Genetics – Genes play a role in the development of autoimmune conditions. The question is how much of a role? This is a hotly debated topic with some researchers proposing as little as 10% and some up to 25-30%.
  2. A trigger – the second factor is the environmental trigger that kicks the autoimmune process into gear. A simple example of one known trigger is gluten in the case of celiac disease. Triggers can come in many shapes and forms. For most autoimmune conditions we are still trying to pin down the trigger. Infections of all kinds are pointed to, food intolerances, chemicals, the list goes on.
  3. Leaky gut – The third factor is impaired tight junctions within the intestine. If intestinal permeability (leaky gut) was not present the ‘trigger’ would pass straight through, either being digested (in the case of gluten) or being eliminated. As I have covered before there are a number of different disease states associated with leaky gut. 

In the words of Dr. Fasano – ‘In many cases, increased intestinal permeability seems to precede disease and causes an abnormality in antigen delivery that triggers the multiorgan process leading to the autoimmune response’

Dr. Fasano goes onto write that the continual exposure to ‘nonself antigens’ or environmental triggers ‘seems to be necessary to perpetuate the process.’ If this is true then it is huge for anyone dealing with an autoimmune condition. Remove the trigger and stop the autoimmune process!

Celiac Disease as a Model For Understanding Autoimmune Disease

Outlined in the paper, celiac disease is used to model this theory on the development of autoimmunity. Unlike many other autoimmune conditions we know the environmental trigger for celiac disease as gluten. We also know the genes that are common among people with celiac disease as HLA genes. The third point, the leaky gut, comes about early in the development of celiac disease when the tight junctions are opened.

When gluten is completely avoided symptoms resolve and the autoimmune markers (antigens) return to normal. This is promising for other autoimmune conditions as it is the first real breakthrough in stopping and reversing an autoimmune condition.

So we know the mechanisms present in celiac disease but does it translate to other autoimmune diseases. According to the (well referenced paper) many other autoimmune conditions are marked by increased intestinal permeability including type 1 diabetes, multiple sclerosis and rheumatoid arthritis.

Food for Thought  

Alessio Fasano has been writing on the subject of autoimmune conditions for many years. For quite awhile his ideas weren’t taken seriously. Recently there has been a growing understanding and appreciation for his theories. If leaky gut is a prerequisite for the development of an autoimmune disease it stands to reason that evaluating what is causing the increased intestinal permeability. The next step would be removing the issue be it a food intolerance, an infection or possibly a chemical exposure and finally repairing the gut.

We are in a promising era. Research, while still being dictated by the pharmaceutical industry, is still making breakthroughs that hint at the bigger picture. Couple the current scientific thinking with an ancestral/evolutionary model and we can start to see that picture more clearly. There’s nothing you can do about your genes but you can eat real whole foods, drink plenty of fresh clean water, exercise appropriately, evaluate any environmental triggers that may be triggering an autoimmune flare and heal your gut.

References and Resources

  1. Leaky Gut and Autoimmune Diseases
  2. Multiple Sclerosis – A Functional View
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