Psyllium Fiber Protects Against Colitis Via Activation of Bile Acid Sensor Farnesoid X Receptor

作者：Alexis Bretin, Jun Zou, Beng San Yeoh, Vu L. Ngo, Shawn Winer, Daniel A. Winer, Lavanya Reddivari, Michael Pellizzon, William Anton Walters, Andrew D. Patterson, Ruth E. Ley, Benoît Chassaing, Matam Vijay–Kumar, Andrew T. Gewirtz · 发表于：Cellular and Molecular Gastroenterology and Hepatology · 年份：2023 · DOI：10.1016/j.jcmgh.2023.02.007 · 被引用次数：49 · 研究领域：Food composition and properties、Polysaccharides and Plant Cell Walls、Gut microbiota and health

BACKGROUND & AIMS: Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to ameliorate 2 chronic inflammatory states, namely, metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter. METHODS: Mice were fed grain-based chow, which is naturally rich in fiber or compositionally defined diets enriched with semi-purified fibers. Mice were studied basally and in models of chemical-induced and T-cell transfer colitis. RESULTS: Relative to all diets tested, mice consuming psyllium-enriched compositionally defined diets were markedly protected against both dextran sulfate sodium- and T-cell transfer-induced colitis, as revealed by clinical-type, histopathologic, morphologic, and immunologic parameters. Such protection associated with stark basal changes in the gut microbiome but was independent of fermentation and, moreover, maintained in mice harboring a minimal microbiota (ie, Altered Schaedler Flora). Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acids (BA) secretion, suggesting that psyllium's known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated level of fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA sequestrant cholestyramine, increased serum BA levels. Moreover, the use of BA mimetic...