%0 Journal Article
%T Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis.
%A Yasuda T
%A Takagi T
%A Asaeda K
%A Hashimoto H
%A Kajiwara M
%A Azuma Y
%A Kitae H
%A Hirai Y
%A Mizushima K
%A Doi T
%A Inoue K
%A Dohi O
%A Yoshida N
%A Uchiyama K
%A Ishikawa T
%A Konishi H
%A Ukawa Y
%A Kohara A
%A Kudoh M
%A Inoue R
%A Naito Y
%A Itoh Y
%J Sci Rep
%V 14
%N 1
%D 2024 07 8
%M 38977770
%F 4.996
%R 10.1038/s41598-024-65791-x
%X 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.