Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.
Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.
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DOI：
10.1016/j.celrep.2017.01.062
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发表时间：
2017-02-14
期刊：
影响因子：
8.8
通讯作者：
Rey FE
中科院分区：
文献类型：
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作者：
Kreznar JH;Keller MP;Traeger LL;Rabaglia ME;Schueler KL;Stapleton DS;Zhao W;Vivas EI;Yandell BS;Broman AT;Hagenbuch B;Attie AD;Rey FE
遗传变异驱动表型多样性并影响代谢性疾病的易感性。在这里，我们描述了8个遗传上不同的近交系小鼠品系在高脂肪/高糖饮食下的代谢表型。我们发现，在不同的小鼠品系之间，糖尿病相关的表型和肠道微生物群组成在应对饮食挑战方面存在显著差异，并确定了与这些特征相关的类群。后续的微生物群移植实验表明，改变肠道微生物群的组成可以改变菌株对饮食诱导的代谢疾病的易感性。动物携带的微生物群落具有增强的加工膳食糖和产生疏水胆汁酸的能力，表现出对代谢疾病的易感性增加。值得注意的是，不同小鼠品系之间葡萄糖刺激的胰岛素分泌的差异通过肠道微生物群转移部分重现。我们的研究结果表明，肠道微生物组有助于在小鼠品系中观察到的遗传和表型多样性，并提供了肠道微生物组与胰岛素分泌之间的联系。宿主遗传学调节代谢疾病的发展，并塑造肠道微生物群的组成。Kreznar等人证明，肠道微生物群有助于菌株对饮食诱导的代谢疾病的易感性，并确定微生物代谢和胰岛素分泌之间的联系。
Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion. Host genetics modulates the development of metabolic disease and shapes the composition of the gut microbiota. Kreznar et al. demonstrate that the gut microbiota contributes to strain-specific susceptibility to diet-induced metabolic disease and identify links between microbial metabolism and insulin secretion.