Autoimmunity Microbiome

Why Autoimmune Diseases Develop

In medicine, the immune system is approached from the basic science level. Its discussed in terms of its details — T cells and macrophages, innate and adaptive immune systems, interleukins and tumor necrosis factor. Very complex stuff, not fully elucidated and hard to relate to the patient sitting in front of you. Its like talking about heart disease by focusing on myocytes and homocysteine – true, essential but hard to connect to human experience.

It wasn’t until I heard Alessio Fassano, MD (MGH pediatric gastroenterologist and celiac researcher) speak at the 2013 International Celiac Disease Symposium that I started to connect the dots. He was talking about celiac disease, but his research on why a GI based disease would cause systemic symptoms was a eureka moment for me. Juvenile arthritis, psoriasis, autoimmune thyroiditis and celiac – of course these weren’t separate diseases in my child but one systemic process. And, once I focused on the forest rather than the trees, I was on the path of understanding how to prevent them in the first place.

Four factors are needed to develop autoimmune disease:

Genes – You have be geneticaly predisposed to develop autoimmune disease. In celiac disease, these genes are known and can be tested but in other autoimmune diseases they may not be. These genes are relatively common but having the gene isn’t enough to develop disease. For example, a third of people have one of the genes for celiac disease, but only 1% of the population actually develops the disease. Thus, a genetic predisposition is necessary to develop autoimmune disease but its not sufficient.

Environmental Triggers – Why are genes turned on in the first place? What are the triggers? Well, this is likely very individual, likely cumulative over time, and likely different triggers for different people. Food supply, environmental toxins, infection, even stress and sleep all have evidence in the medical literature that they can affect autoimmune diseases. Like drops filling a cup until finally one day the cup overflows. Some studies show 2/3rd of the blame for developing autoimmune disease.

My gut tells me that this is what the issue is. DM1 doubling in prevelance every 20 years, this is too fast for “genetic drift” to be the cause. Something in our environment is doing this.

Intestinal Permeability – Say the words “leaky gut” and most physicians are immediately biased to think you are a quack. I know, because I would have been the first to roll my eyes. But do the work/read the literature, you’ll realize that intestinal permeability (doesn’t that sound less cray-cray?) is validated/supported by strong evidence in the medical literature. At the DDW meeting this week, I was shocked by the majority of physicians who are now accepting this once-quack idea.

The walls of your intestine are made up of a layer of cells. Between the cells, sort of like the grout between the tiles, are the “tight junctions”, which control what passes from the intestine into the bloodstream (and therefore disperses throughout your body). In 2000, Dr Fasano discovered zonulin. More zonulin, more “leaky” – bigger proteins pass thru. These proteins like foreign invaders, so your immune system comes and attacks, taking out the cells of your body as well.

The concept of intestinal permeability is best understood now in celiac disease, but also issue in other AI syndromes such as MS, AS, UC/Chrons, DM1, Hashimoto’s, even autism. List is growing as more studied. Its necessary componenet of autoimmune disease. So, if you want to heal AI, you need to heal your leaky gut. Growing understanding within medicine, although just beginning to permeate up from research world to teaching institutions and practicing clinicians.

Microbiome Changes – this is a hot topic in medicine right now, with a flurry of research activity. We know that the microbiome, those trillions of bacteria, viruses, and fungi that live mostly on the lining of your intestines, is changed in autoimmune disease as well as other disease states. Relationship to diet and other environmental exposures, because just as we are what we eat, our microbiome is what we feed it. We are beginning to understand its complexity but have more questions than answers. What is a healthy microbiome? Are the changes seen in autoimmune disease a cause, an effect or an association without causation? And can we change our microbiome composition? Will that affect our health outcome?

So, those are the four necessary components underlying the development of autoimmune disease. Our DNA is what it is, but we do exert some control over the other three factors: our environmental exposures and, through diet, our gut health (intestinal permeability and our microbiome).  So maybe this is where we can start in the fight against autoimmune diseases, with investigating the evidence behind the impact of diet and environment on autoimmunity.

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