PSYLLIUM FIBER PROTECTS AGAINST COLITIS VIA ACTIVATON OF BILE ACID RECEPTOR FXR

Objective: Fiber-rich foods promote health but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had a uniquehad unique ability to ameliorate 2 chronic inflammatory states, namely metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter. Design: Mice were fed grain-based chow (GBC), which is naturally rich in fiber or compositionally-defined diets (CDD) 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 CDD, were markedly protected against both DSS- and T-cell transfer-induced colitis as assessed by clinical-type, histopathologic, morphologic, or immunologic parameters. Such protection associated with stark basal changes in the microbiome but was independent of fermentation and, moreover, maintained in mice with a minimal microbiome; i.e. Altered Schaedler Flora. Transcriptomic analysis revealed psyllium's induced expression of genes mediating bile acid (BA) secretion suggesting psyllium's known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA chelator cholestyramine, increased serum BA levels. Moreover, use of BA mimetics that activate the FXR BA receptor and FXR-KO mice suggested that activation of FXR was necessary and sufficient for psyllium's protection against colitis. Conclusions: Psyllium protects against colitis via altering BA metabolism leading to activation of FXR.