Interactions between gut microbiota, host genetics and diet in the development of metabolic syndrome. Interactions between gut microbiota, host genetics and diet in the development of metabolic syndrome

Obesity, diabetes and metabolic syndrome are the results of complex interactions between genetic and environmental factors, including the gut microbiota. To dissect interactions between the gut microbiota, diet and genetic background, we utilized three inbred strains of mice, which differ in development of obesity and metabolic syndrome, plus three derivative lines generated by breeding these strains in a common environment. Analysis of metabolic parameters and gut microbiota in the inbred strains and their environmentally normalized derivatives revealed strong interactions between the microbiota, diet, environmental history and metabolic phenotypes. Some phenotypes could be transferred to germ-free recipient animals by fecal transplant. Strong strain-dependent and strain-independent correlations were found between specific microbes and metabolic phenotypes. Environmental reprogramming of the microbiota resulted in one obesity-prone strain becoming obesity-resistant. Thus, in mice, development of obesity/metabolic syndrome is the result of strong interactions between the gut microbiota, host genetics and diet. In permissive genetic backgrounds, environmental reprograming of the microbiota can ameliorate development of metabolic syndrome.

肥胖、糖尿病与代谢综合征（metabolic syndrome）是遗传与环境因素（包括肠道菌群（gut microbiota））之间复杂相互作用的产物。为解析肠道菌群、饮食与宿主遗传背景之间的相互作用机制，本研究选用3株在肥胖与代谢综合征发病特征上存在显著差异的近交系小鼠（inbred strains of mice），并辅以通过将这些品系在统一环境中繁育得到的3个衍生株系。对近交品系及其经环境标准化处理的衍生株系的代谢参数与肠道菌群开展分析后，结果显示菌群、饮食、环境暴露史与代谢表型之间存在强烈相互作用。部分代谢表型可通过粪便移植（fecal transplant）传递给无菌受体动物（germ-free recipient animals）。研究发现，特定微生物类群与代谢表型之间存在较强的品系依赖性与非品系依赖性关联。对菌群实施环境重编程后，1株易肥胖品系转变为抗肥胖型。综上，在小鼠模型中，肥胖/代谢综合征的发生是肠道菌群、宿主遗传与饮食三者间强烈相互作用的结果；在允许性遗传背景下，对菌群进行环境重编程可改善代谢综合征的发生发展。