If you have a digestive disorder, such as celiac disease, Crohn’s disease, or irritable bowel syndrome (IBS), chances are you will sooner or later come across the word “zonulin.” Since its discovery in the year 2000, zonulin has become a hot topic of interest to researchers, doctors, patients, and bloggers. In one sentence, zonulin is a protein produced in the human intestine that helps regulate intestinal permeability. Some is needed, but over-expression of zonulin is bad and may contribute to leaky gut.
The first report of zonulin was published in a highly esteemed medical journal, The Lancet.[i] A group of researchers led by Dr. Alessio Fasano at the University of Maryland began with studies on a toxin that is produced by Vibrio cholerae, the bacteria that causes cholera. The classic symptom of cholera is profuse, watery, debilitating diarrhea. One of the bacterial toxins associated with cholera, called zonula occludens toxin, rapidly and reversibly opens the tight junctions between intestinal cells, temporarily causing leaky gut. Dr. Fasano and his colleagues found that cells in the human intestine produce a protein that is almost identical to the zonula occludens toxin, and they named it zonulin. Dr. Fasano’s group then isolated zonulin from human intestines and found it to increase intestinal permeability in primates.[ii]
When we say that zonulin increases intestinal permeability, it is helpful to think of the lining of the intestines as like a cheesecloth. Only the tiniest particles should pass through. Zonulin makes the holes of the cheesecloth bigger and allows large particles to pass into the bloodstream and through the body. We call this increased intestinal permeability, or leaky gut. The process of leaky gut is thought to contribute to inflammation throughout the body and even to the development of autoimmune disease.
Consistent with the theory of leaky gut and autoimmune disease, excess zonulin production is found in a variety of autoimmune diseases. It is also found during flare-ups of celiac disease.[iii] Whether a person has an autoimmune disease or not, the 2 most important triggers for zonulin release are bacteria and gluten. Even in people who do not have celiac disease, the gluten and gliadin proteins that are found in wheat can trigger the release of zonulin and increase intestinal permeability.[iv]
As we learn more and more about functional gastrointestinal disorders, we will learn more and more about the biochemistry that affects them. Zonulin gives us one explanation for how diet might contribute to a leaky gut. If we eliminate gluten from the diet, we eliminate one potential trigger for excessive zonulin release. This might help to prevent a leaky gut, or it might allow an already leaky gut the chance to heal.
[ii] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91(1):151-175.
[iii] Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355(9214):1518-1519.
[iv] Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006;41(4):408-419.