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Abstract:
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 two 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 (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 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; i.e. Altered Schaedler Flora. Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acid (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 mimetics that activate the FXR, as well as the use of FXR-KO mice, suggested that activation of FXR plays a central role in psyllium's protection against colitis.
Conclusions: Psyllium protects against colitis via altering BA metabolism resulting in activation of FXR, which suppresses pro-inflammatory signaling.
