Format

Send to

Choose Destination
Nat Commun. 2019 Jan 9;10(1):89. doi: 10.1038/s41467-018-07859-7.

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

Author information

1
Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
2
Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India.
3
Centre for Cellular and Molecular Platforms (C-CAMP), GKVK campus, Bangalore, Karnataka, 560065, India.
4
Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA.
5
Department of Pharmacology, Dalhousie University, Halifax, B3H 4R2, Nova Scotia, Canada.
6
Computer Engineering and Computer Science, Kentucky Biomedical Research Infrastructure Network, University of Louisville, Louisville, KY, 40202, USA.
7
Department of Medicine, University of Louisville, Louisville, KY, 40202, USA.
8
Department of Pathology, University of Louisville, Louisville, KY, 40202, USA.
9
Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India. praveenv@instem.res.in.
10
Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA. jvrao001@louisville.edu.

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.

PMID:
30626868
DOI:
10.1038/s41467-018-07859-7

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center