RRC ID 81128
Author Yasuda T, Takagi T, Asaeda K, Hashimoto H, Kajiwara M, Azuma Y, Kitae H, Hirai Y, Mizushima K, Doi T, Inoue K, Dohi O, Yoshida N, Uchiyama K, Ishikawa T, Konishi H, Ukawa Y, Kohara A, Kudoh M, Inoue R, Naito Y, Itoh Y.
Title Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis.
Journal Sci Rep
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.
Volume 14(1)
Pages 15706
Published 2024-7-8
DOI 10.1038/s41598-024-65791-x
PII 10.1038/s41598-024-65791-x
PMID 38977770
PMC PMC11231190
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Colitis* / chemically induced Colitis* / metabolism Colon / metabolism Coumarins* / pharmacology Dextran Sulfate Gastrointestinal Microbiome Humans Intestinal Barrier Function Intestinal Mucosa* / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Mucin-2 / genetics Mucin-2 / metabolism NF-E2-Related Factor 2* / metabolism Receptors, Aryl Hydrocarbon* / metabolism Signal Transduction / drug effects
Resource
Mice RBRC01390