Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis.
Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis.
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DOI：
10.1194/jlr.m072165
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发表时间：
2017-03
影响因子：
6.5
通讯作者：
Hirata KI
中科院分区：
文献类型：
--
作者：
Kasahara K;Tanoue T;Yamashita T;Yodoi K;Matsumoto T;Emoto T;Mizoguchi T;Hayashi T;Kitano N;Sasaki N;Atarashi K;Honda K;Hirata KI
肠道微生物群被证明在动脉粥样硬化的发展中起关键作用，但详细的机制是有限的。本研究的目的是阐明肠道微生物群通过脂质代谢和全身炎症对动脉粥样硬化的影响。无菌或常规饲养（Conv） ApoE缺陷（ApoE−/−）小鼠喂食鼠粮并在20周龄时安乐死。我们发现，与Conv ApoE - / -小鼠相比，ApoE - / -小鼠肠道微生物群的缺乏导致血浆和肝脏胆固醇水平显著升高。肠道菌群的缺失改变了回肠中胆汁酸的组成，这与肠肝成纤维细胞生长因子15、成纤维细胞生长因子受体4轴的激活、胆固醇7α-羟化酶和肝脏胆汁酸合成的减少有关，导致肝脏胆固醇含量的积累。然而，我们发现，与Conv ApoE - / -小鼠相比，缺乏微生物群导致动脉粥样硬化病变形成显著减少，这可能与脂多糖介导的炎症反应的衰减有关。我们的研究结果表明，肠道微生物群影响小鼠的高胆固醇血症和动脉粥样硬化。
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE−/−) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE−/− mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE−/− mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE−/− mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.