Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway
| Autor: | Morgan G. I. Langille, Eric C. Rouchka, Gavin M. Douglas, Taslimarif Saiyed, Gerald W. Dryden, Sobha R. Bodduluri, Paresh Patel, Praveen Kumar Vemula, Huang-Ge Zhang, Matam Vijay-Kumar, Ankita A. Hiwale, Sandeep Chandrashekharappa, Bindu Hegde, Becca V. Baby, Xi Cheng, Venkatakrishna R. Jala, Sabine Waigel, Bodduluri Haribabu, Rajbir Singh, Houda Alatassi, Niranjan G. Kotla |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy 02 engineering and technology Gut flora Mice Coumarins Basic Helix-Loop-Helix Transcription Factors Intestinal Mucosa lcsh:Science Mice Knockout Multidisciplinary biology Tight junction Chemistry digestive oral and skin physiology 021001 nanoscience & nanotechnology Specific Pathogen-Free Organisms 3. Good health Gut Epithelium Cell biology medicine.symptom 0210 nano-technology HT29 Cells NF-E2-Related Factor 2 Science Inflammation Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Humans Colitis Tight Junction Proteins Macrophages Epithelial Cells General Chemistry medicine.disease Aryl hydrocarbon receptor biology.organism_classification Urolithin Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Receptors Aryl Hydrocarbon Caco-2 biology.protein lcsh:Q Caco-2 Cells |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-18 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-07859-7 |
| Popis: | 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. Urolithins are microbial metabolites derived from food polyphenols. Here, Singh et al. show that urolithin A and a synthetic analogue enhance gut barrier function via Nrf2-dependent pathways and mitigate inflammation and colitis in mice, highlighting a potential application for inflammatory bowel diseases. |
| Databáze: | OpenAIRE |
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