{Reference Type}: Journal Article
{Title}: Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis.
{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;
{Journal}: Sci Rep
{Volume}: 14
{Issue}: 1
{Year}: 2024 07 8
{Factor}: 4.996
{DOI}: 10.1038/s41598-024-65791-x
{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.