Physiopathology of intestinal barrier and the role of zonulin

The intestinal epithelium with its barrier function controls the antigen trafficking from the intestinal lumen to the submucosa. Zonulin, a precursor of haptoglobin-2, plays a key role in maintaining the homeostasis of the intestinal mucosa through the regulation of tight junctions, cell-cell junctions responsible of the influx of dietary and microbial antigens via paracellular mute of intestinal absorption. Several studies have observed an association between zonulin levels and alteration of intestinal permeability. It is assumed that in genetically predisposed individuals, an altered intestinal permeability may induce an increased exposure to luminal antigens with consequent loss of immune tolerance, thus leading to the development and progression of various chronic inflammatory disorders. Here, we review the mechanism of intestinal permeability regulation by zonulin and the related pathophysiological implications.