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Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Fasano, Alessio·2011·Physiological Reviews

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.

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Metadata

Authors
Fasano, A.
Venue
Physiological Reviews
Published
2011-01
Volume
91
Issue
1
Pages
151-175
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
OpenAlex
W2131691531
Cited by
1,003
References
12
FWCI
4.12
Type
journal article
Language
en
Open access
closed

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Fasano, A. (2011). Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. https://doi.org/10.1152/physrev.00003.2008

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