膳食糖引起的微生物群失衡會破壞免疫介導的代謝綜合征保護
Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome
（Cell；IF:66.85）
- Kawano Y, Edwards M, Huang Y, et al. Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. Cell. 2022
- CORRESPONDENCE TO : ii2137@cumc.columbia.edu
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.
腸道微生物調節代謝綜合征的機制尚不完全明確。我們的研究表明腸道微生物群通過誘導共生特異性 Th17 細胞來防止肥胖、代謝綜合征和糖尿病前期表型的發展。高脂肪、高糖飲食通過消耗 Th17 誘導微生物以及共生 Th17 細胞儲存的保護作用這一方式促進代謝疾病。微生物群誘導的 Th17 細胞以 IL-17 依賴性的方式調節腸道上皮細胞的脂質吸收來提供保護。飲食誘導的保護性 Th17 細胞喪失是由糖介導的。從高脂肪飲食中消除糖分可以保護小鼠免受肥胖和代謝綜合征的影響，這種方式依賴於共生特異性 Th17 細胞。糖和 ILC3 促進了嚙齒動物糞菌的生長，從而取代了誘導 Th17 的微生物群。這些結果定義了構成代謝綜合征風險的飲食和微生物群因素，同時還定義了膳食糖的免疫致病性的微生物群依賴性機制，並突出了飲食、微生物群和腸道免疫在調節代謝紊亂中的複雜相互作用。
