Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal Homeostasis through Regulation of Interleukin-10 Receptor.

Autor:	Alexeev EE; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado., Lanis JM; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado., Kao DJ; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado., Campbell EL; Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom., Kelly CJ; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado., Battista KD; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado., Gerich ME; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado., Jenkins BR; Department of Microbiology and Immunology, Montana State University, Bozeman, Montana., Walk ST; Department of Microbiology and Immunology, Montana State University, Bozeman, Montana., Kominsky DJ; Department of Microbiology and Immunology, Montana State University, Bozeman, Montana. Electronic address: douglas.kominsky@montana.edu., Colgan SP; Mucosal Inflammation Program and Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado. Electronic address: sean.colgan@ucdenver.edu.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2018 May; Vol. 188 (5), pp. 1183-1194. Date of Electronic Publication: 2018 Feb 16.
DOI:	10.1016/j.ajpath.2018.01.011
Abstrakt:	Interactions between the gut microbiota and the host are important for health, where dysbiosis has emerged as a likely component of mucosal disease. The specific constituents of the microbiota that contribute to mucosal disease are not well defined. The authors sought to define microbial components that regulate homeostasis within the intestinal mucosa. Using an unbiased, metabolomic profiling approach, a selective depletion of indole and indole-derived metabolites was identified in murine and human colitis. Indole-3-propionic acid (IPA) was selectively diminished in circulating serum from human subjects with active colitis, and IPA served as a biomarker of disease remission. Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. Colonization of germ-free mice with wild-type Escherichia coli, but not E. coli mutants unable to generate indole, induced colonic epithelial IL-10R1. Moreover, oral administration of IPA significantly ameliorated disease in a chemically induced murine colitis model. This work defines a novel role of indole metabolites in anti-inflammatory pathways mediated by epithelial IL-10 signaling and identifies possible avenues for utilizing indoles as novel therapeutics in mucosal disease. (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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