Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway.

Autor:	Singh R; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA., Chandrashekharappa S; Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India., Bodduluri SR; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA., Baby BV; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA., Hegde B; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA., Kotla NG; Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India., Hiwale AA; Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India., Saiyed T; Centre for Cellular and Molecular Platforms (C-CAMP), GKVK campus, Bangalore, Karnataka, 560065, India., Patel P; Centre for Cellular and Molecular Platforms (C-CAMP), GKVK campus, Bangalore, Karnataka, 560065, India., Vijay-Kumar M; Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Langille MGI; Department of Pharmacology, Dalhousie University, Halifax, B3H 4R2, Nova Scotia, Canada., Douglas GM; Department of Pharmacology, Dalhousie University, Halifax, B3H 4R2, Nova Scotia, Canada., Cheng X; Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Rouchka EC; Computer Engineering and Computer Science, Kentucky Biomedical Research Infrastructure Network, University of Louisville, Louisville, KY, 40202, USA., Waigel SJ; Department of Medicine, University of Louisville, Louisville, KY, 40202, USA., Dryden GW; Department of Medicine, University of Louisville, Louisville, KY, 40202, USA., Alatassi H; Department of Pathology, University of Louisville, Louisville, KY, 40202, USA., Zhang HG; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA., Haribabu B; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA., Vemula PK; Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India. praveenv@instem.res.in., Jala VR; Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA. jvrao001@louisville.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2019 Jan 09; Vol. 10 (1), pp. 89. Date of Electronic Publication: 2019 Jan 09.
DOI:	10.1038/s41467-018-07859-7
Abstrakt:	The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.
Databáze:	MEDLINE
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