Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

Alessio Fasano M.D.

Abstract

The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function 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 tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions 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 genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional 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 intestinal barrier function. This review is timely given the increased interest in the role of a “leaky gut” in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

Source Mucosal Biology Research Center and Center for Celiac Research, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. afasano@mbrc.umaryland.edu

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2 Responses to Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

  1. Pingback: Have you CHALLENGED yourself today? « Minnesota Strength & Conditioning

  2. Dan Baruch says:

    “With celiac disease, we could never understand how a big protein like gluten was getting through to the immune system. Now we have the answer,” explains Dr. Fasano. “People with celiac have an increased level of zonulin, which opens the junctions between the cells. In essence, the gateways are stuck open, allowing gluten and other allergens to pass. Once these allergens get into the immune system, they are attacked by the antibodies,” adds Dr. Fasano.

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