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

Autor:	Bretin A; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia., Zou J; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia., San Yeoh B; University of Toledo Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio., Ngo VL; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia., Winer S; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Winer DA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Buck Institute for Research on Aging, Novato, California., Reddivari L; Department of Food Science, Purdue University, West Lafayette, Indiana., Pellizzon M; Research Diets, Inc., New Brunswick, New Jersey., Walters WA; Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany., Patterson AD; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania., Ley R; Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany., Chassaing B; INSERM U1016, Team 'Mucosal Microbiota in Chronic Inflammatory Diseases,' CNRS UMR 8104, Université Paris Cité, Paris, France., Vijay-Kumar M; University of Toledo Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio., Gewirtz AT; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia. Electronic address: agewirtz@gsu.edu.
Jazyk:	angličtina
Zdroj:	Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2023; Vol. 15 (6), pp. 1421-1442. Date of Electronic Publication: 2023 Feb 23.
DOI:	10.1016/j.jcmgh.2023.02.007
Abstrakt:	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 mimetics that activate the farnesoid X receptor (FXR), as well as the use of FXR-knockout 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. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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