Authors: Yoshinaga Kawano, Madeline Edwards, Yiming Huang, Angelina M. Bilate, Leandro P. Araujo, Takeshi Tanoue, Koji Atarashi, Mark S. Ladinsky, Steven L. Reiner, Harris H. Wang, Daniel Mucida, Kenya Honda, Ivaylo I. Ivanov (2022)
Abstract:
How intestinal microbes regulate metabolic syndrome is incompletely understood. We show that intestinal microbiota protects against development of obesity, metabolic syndrome, and pre-diabetic phenotypes by inducing commensal-specific Th17 cells. High-fat, high-sugar diet promoted metabolic disease by depleting Th17-inducing microbes, and recovery of commensal Th17 cells restored protection. Microbiota-induced Th17 cells afforded protection by regulating lipid absorption across intestinal epithelium in an IL-17-dependent manner. Diet-induced loss of protective Th17 cells was mediated by the presence of sugar. Eliminating sugar from high-fat diets protected mice from obesity and metabolic syndrome in a manner dependent on commensal-specific Th17 cells. Sugar and ILC3 promoted outgrowth of Faecalibaculum rodentium that displaced Th17-inducing microbiota. These results define dietary and microbiota factors posing risk for metabolic syndrome. They also define a microbiota-dependent mechanism for immuno-pathogenicity of dietary sugar and highlight an elaborate interaction between diet, microbiota, and intestinal immunity in regulation of metabolic disorders.
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