COVID-19 Response: Local Logistics     National Effort

Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway [Discovery to Innovation Accelerator]

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TitleEnhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway [Discovery to Innovation Accelerator]
Publication TypeJournal Article
Year of Publication2019
AuthorsSingh R, Chandrashekharappa S, Bodduluri SR, Baby BV, Hegde B, Kotla NG, Hiwale AA, Saiyed T, Patel P, Vijay-Kumar M, Langille MGI, Douglas GM, Cheng X, Rouchka EC, Waigel SJ, Dryden GW, Alatassi H, Zhang H-G, Haribabu B, Vemula PK, Jala VR
JournalNat Commun
Volume10
Issue1
Pagination89
Date Published2019 Jan 09
ISSN2041-1723
Abstract

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.

DOI10.1038/s41467-018-07859-7
Alternate JournalNat Commun
PubMed ID30626868