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Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis.
- Source :
-
Scientific reports [Sci Rep] 2024 Jul 08; Vol. 14 (1), pp. 15706. Date of Electronic Publication: 2024 Jul 08. - Publication Year :
- 2024
-
Abstract
- Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Mucin-2 metabolism
Mucin-2 genetics
Humans
Colon metabolism
Mice, Inbred C57BL
Signal Transduction drug effects
Male
Gastrointestinal Microbiome
Mice, Knockout
Dextran Sulfate
Basic Helix-Loop-Helix Transcription Factors metabolism
Basic Helix-Loop-Helix Transcription Factors genetics
Intestinal Barrier Function
NF-E2-Related Factor 2 metabolism
Receptors, Aryl Hydrocarbon metabolism
Intestinal Mucosa metabolism
Coumarins pharmacology
Colitis metabolism
Colitis chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 38977770
- Full Text :
- https://doi.org/10.1038/s41598-024-65791-x