Zonulin explains it all

Weight Loss

autistic spectrum disorder

Brace yourself for a somewhat more complex conversation, but one that is SO important for our understanding of diet and health.

We know that the gliadin protein of wheat and related grains (e.g., secalin in rye, hordein in barley, zein in corn) initiate a complex series of events in the lining of the intestines that increases intestinal permeability. Detailed and elegant investigations, including that by Dr. Alessio Fasano while at University of Maryland and now at Harvard, have shown that gliadin initiates an increase in intestinal permeability, an effect mediated by the zonulin protein that causes disassembly of the tight junctions between intestinal cells that normally provides a barrier against the entry of foreign materials into the intestinal wall and bloodstream.

According to Dr. Fasano, “The inappropriate production of increased amount of zonulin causes a loss of barrier function, with subsequent inappropriate and uncontrolled antigen trafficking instigating an innate immune response by the submucosal immune compartment. If this process continues, an adaptive immune response is mounted causing production of pro-inflammatory cytokines, including IFN-γ and TNF-α that cause further opening of the paracellular pathway to the passage of antigens, creating a vicious cycle.” In other words, the gliadin protein of wheat opens the floodgates to antigens that trigger inflammation and abnormal autoimmune responses.

Increased blood levels of zonulin have now been measured in people who are obese, have insulin resistance, type 1 and type 2 diabetes, multiple sclerosis, autistic spectrum disorder, inflammatory bowel disease, polycystic ovary syndrome, celiac disease, asthma, even coronary disease. In short, the underlying reasons to explain why wheat and grain consumption are associated with an astounding list of common diseases is becoming clearer and clearer. The science tells us that consumption of wheat and grains, the foods we are urged to consume every meal, every day, by every agency in the business of providing dietary advice, invites increased zonulin and intestinal permeability that lead to numerous common health conditions.


The two major triggers of zonulin release that have been described so far are bacteria and gliadin.”

                                                                                                                                      Drs.  C. Sturgeon and A. Fasano


Wheat and grains, via the protein gliadin, therefore increase zonulin levels in the intestinal lining and blood that, in turn, increase intestinal permeability and thereby inflammation and autoimmunity.

What else increases zonulin and thereby intestinal permeability? Bacteria, but especially so-called Gram-negative Enterobacteriaceae such as E. coli, Shigella, Campylobacter, Pseudomonas and others. Gram-negative Enterobacteriaceae, you may recall, are the species that dominate in small intestinal bacterial overgrowth, SIBO.

Here’s a question that has not been thoroughly explored yet: If the gliadin of wheat increases zonulin and intestinal permeability, and SIBO likewise increases zonulin and intestinal permeability, what happens when BOTH are present concurrently? I believe it is safe to say that an explosive increase in zonulin and intestinal permeability develops. And that is the situation that applies to so many people, wondering why they eat plenty of “healthy whole grains” but have to deal with fibromyalgia, irritable bowel syndrome symptoms, Hashimoto’s thyroiditis, rheumatoid arthritis, ulcerative colitis, Crohn’s disease, weight gain, type 2 diabetes, depression . . .

Couple all this with the increase in SIBO and in zonulin with aging and you can readily appreciate that, over a lifetime, we are increasingly susceptible to all the diseases of intestinal permeability from diabetes to dementia. The solution? Eat no wheat nor grains, address dysbiosis and SIBO, the factors that determine intestinal permeability.


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