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Volume 4 Issue 6

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Abby's Magazine - Volume 4 Issue 6 | Page 13 Zonulin ? What is Zonulin is a protein that modulates the permeability of ght junc ons between cells of the wall of the diges ve tract. It was discovered in 2000 by Alessio Fasano and his team at the University of Maryland School of Medicine. As the mammalian analogue of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae, zonulin has been implicated in the pathogenesis of coeliac disease and diabetes mellitus type 1. Gliadin (glycoprotein present in wheat) ac vates zonulin signaling irrespec ve of the gene c expression of autoimmunity, leading to increased intes nal permeability to macromolecules. Zonulin Regulation neuroendocrine network, the intes nal epithelial barrier, with its intercellular ght junc ons, controls the equilibrium between tolerance and immunity to non-self an gens. Zonulin is the only physiological modulator of intercellular ght junc ons described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in gene cally suscep ble individuals, both intes nal and extraintes nal autoimmune, inflammatory, and neoplas c disorders can occur. This new paradigm subverts tradi onal theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intes nal barrier func on. This review is mely given the increased interest in the role of a "leaky gut" in the pathogenesis of several pathological condi ons targe ng both the intes ne and extraintes nal organs. Zonulin and its regula on of intes nal barrier func on: the biological door to inflamma on, autoimmunity, and cancer. The primary func ons of the gastrointes nal tract have tradi onally been perceived to be limited to the diges on and absorp on of nutrients and to electrolytes and water homeostasis. A more a en ve analysis of the anatomic and func onal arrangement of the gastrointes nal tract, however, suggests that another extremely important func on of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid ssue and the

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