Zonulin is a protein, synthesized in intestinal and liver cells, that reversibly regulates intestinal permeability. Zonulin modulates the permeability of tight junctions between cells of the wall of the digestive tract. It was discovered in 2000 by Alessio Fasano and his team at the university of maryland school of medicine. 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.