Leaky gut and autoimmune diseases

Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Clinical Reviews in Allergy & Immunology (Impact Factor: 4.73). 11/2011; 42(1):71-8. DOI: 10.1007/s12016-011-8291-x
Source: PubMed

ABSTRACT Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. 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 physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune 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 re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

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Available from: Alessio Fasano, Jan 06, 2014
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    • "The presented facts can give some clues for biological investigation of the me­ chanism of T1D development, but hardly any as­ sumption about the top trigger's identity. There is no other food type found having conclusive causative relations with T1D (Knip, Simel, 2012), although theories exist that wheat proteins may much contribute to the leaky gut (intestinal per­ meability), allowing protein macromolecules to pass through the intestinal epithelium into the bloodstream (Fasano, 2012). Additionally, a simple fact that T1D is com­ mon among the youngest population (0 + years) helps to further confine the description of the trig­ ger, as more likely bringing an occasional sharply affecting encounter than systemically accumulated through life exposure series. "
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    01/2015; 2015:1-12. DOI:10.1155/2015/636207
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    • "''Leaky gut'' syndrome ''Leaky Gut'' Syndrome is a term given to the condition where the epithelial barrier function of the small or large intestine is impaired , causing less discrimination in the numbers and types of molecules and cells that are able to pass from the gut to the circulatory system and vice versa [32] [33] [34]. Tight junctions are responsible for the epithelial barrier function, and consist of a system of several proteins in the paracellular space between each cell in the gut lining. "
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