What is causing this gluten mess? 

We know that a loss of immune tolerance predates disease onset. Why do we lose tolerance? Bear with me here as this section is the key to making the leap to understanding this conundrum and why a change may be necessary.

Here we need to look at the science: In the case of celiac disease, we know that humans that carry genes for the human leukocyte antigen DQ2 and DQ8 are the ones at risk for developing celiac disease. What is fascinating is that many people with the HLA DQ2/8 genotype never develop the disease. Why would this be?

The gut micro biome and intestinal permeability or what is called a leaky gut appears to be the answer. Humans that have a diverse and intact microbial garden in their gut do not develop disease at the same rate compared to humans with a poorly developed bacterial system.

The micro biome exists primarily inside the gastrointestinal tract. This intestinal lining is one cell layer thick and is arranged like soldiers in a wall making a tube that is hollow and exposed to the outside world via our nose and mouth. These cells are held together by proteins called occludins and claudins that make up a tight junction set in place to prevent pathogens and food proteins from invading the immune system’s home.

According to Harvard pediatric gastroenterologist and celiac expert Dr. Alessio Fasano, patients with celiac disease, non celiac gluten sensitivity, autism and other autoimmune diseases have an increase in a chemical called zonulin that opens the tight junctions, the space between the intestinal cells, allowing for leakage of proteins into a forbidden zone. This is the moment at which we lose tolerance and develop disease.

First degree relatives of patients with autoimmune diseases also have elevated levels of zonulin proteins albeit lower than the ill relative but much higher than a healthy control subject proving the genetic linkage.

The two main triggers for increasing zonulin appear to be intestinal dysbiosis (abnormal bacteria in the gut) and gluten.

According to Dr. Fasano, gluten is seen by the immune system as a component of a microorganism. That is to say that it is seen as a bacteria. This is a remarkable reality as food proteins should not be recognized in this way.

In a 2013 study from the Mayo clinic on irritable bowel syndrome and gluten ingestion, the authors found that irrespective of one’s gluten susceptibility genotype, all humans react with inflammation to gluten proteins. This is amazing and follows the mice research from last week. Our favorite food triggers a mild inflammatory reaction in our white blood cells.

Putting this into perspective, if your gut has inflammatory reactions to gluten, your genetic makeup codes for an increase in zonulin and your microbial flora are dysfunctional, then you are ripe for disease. The current thinking is that based on the following negative gut influences, our gut micro biome is messed up as a population, leading to risk:

1) Caesarian delivery

2) Formula feeding with cow based milk

3) Recurrent antibiotic exposure

4) High refined flour, high refined sugar diet, high fat, low fiber diet

5) Chronic drug use: antacids, non steroidal anti inflammatories, steroids

6) Chronic consumption of non-nutritive sweeteners like saccharin

7) Chronic alcohol abuse

8) Chronic stress

Modern American life has set some of us up to not handle gluten proteins appropriately. The bacteria that reside within us now have become dysfunctional and no longer perform the protective functions of securing the tight junctions, keeping a mucous layer intact and providing food for the gut cells.

Whether it is a viral gastroenteritis, repeated antibiotic use, antacid use, an American style processed diet or gluten that causes a disruption, the bottom line yet again appears to be that we need to keep our friendly bacteria healthy and functional.

To reiterate, Dr. Fasano’s research has shown us that gluten proteins, especially gliadin, directly up regulates the protein zonulin by binding the receptor cxcr-7 which causes increased intestinal permeability at the tight junctions and a loss of tolerance to food proteins.

I think that the case is becoming more worrisome from the research showing that gluten is irritating more of us than previously thought, because of the micro biome damage. It is worse if you have a genetic predisposition to immune reactions as stated, but may truly affect all of us at some level.

Back to my personal story. I think at some point in my life I became sensitive to gluten proteins and my disease risk changed. My 20s and 30s were not a time of great nutrition and stress control, thus ushering in risk factors for an unstable gut micro biome and gluten reactivity. Scientifically, it is a stretch to say that my entire cardiac risk was eliminated by going gluten free, however, the timing of the resolution of my abnormal lipid profile and my overall health is hard to ignore.

A hypothesis is the beginning point for a rule or law. I believe that in a subset of humans, myself included, bacterial dysbiosis of the micro biome leads to gluten sensitivity and ultimately inflammation and cardiac risk. Remember that patients with celiac disease have double the risk of heart disease. Gluten is a part of this problem. To what extent remains to be seen.

Keeping the micro biome robust and diverse likely has a protective affect against reacting to any food, including gluten. Humans have historically had better biodiversity before the advent of the risk factors listed above. The issues with gluten seem to be increasing, and this would parallel the dysfunction of the human micro biome.

Take home point: What we do know is that if we have a stable gut micro biome that contains beneficial bacteria producing signals to increase the claudins and occludins thereby keeping our intestinal tight junctions strong, we will not suffer these issues to the same degree.

How do we do this?

To be continued.

Dr. Chris Magryta is a physician at Salisbury Pediatric Associates. Contact him at newsletter@salisburypediatrics.com