Yoshinaga Kawano, et al.

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 commensalspecific 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.