Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Rajbir Singh, Sandeep Chandrashekharappa, Sobha R. Bodduluri, Becca V. Baby, Bindu Hegde, Niranjan G. Kotla, Ankita A. Hiwale, Taslimarif Saiyed, Paresh Patel, Matam Vijay-Kumar, Morgan G. I. Langille, Gavin M. Douglas, Xi Cheng, Eric C. Rouchka, Sabine J. Waigel, Gerald W. Dryden, Houda Alatassi, Huang-Ge Zhang, Bodduluri Haribabu, Praveen K. Vemula, Venkatakrishna R. Jala

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. More... »

PAGES

89

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-07859-7

    DOI

    http://dx.doi.org/10.1038/s41467-018-07859-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111102131

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30626868


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