BACKGROUND Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale. RESULTS We depleted the intestinal microbiota of hypercholesterolemic female Apoe-/- mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa. CONCLUSIONS These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.

中文翻译：

---

肠道菌群调节宿主胆固醇的稳态。

背景技术血液胆固醇的管理是预防心血管疾病的主要工作重点。这项研究的目的是研究肠道菌群如何在生物体规模上影响宿主胆固醇的体内稳态。结果我们使用广谱抗生素消除了高胆固醇血症雌性Apoe-/-小鼠的肠道菌群。通过补充方法测量血浆胆固醇水平以及胆固醇合成和通量表明，肠道菌群强烈调节血浆胆固醇水平，肝脏胆固醇合成和肝肠循环。而且，将微生物群从血浆胆固醇水平升高的人类移植到受体小鼠后，会引起血浆胆固醇水平升高的表型，同时肝胆固醇合成水平较低且肠道吸收模式较高。收件人小鼠的表型与贝塔蛋白菌，阿利培斯，拟杆菌和Barnesiella类群的几种特定细菌系统型有关。结论这些结果表明，肠道菌群决定了循环胆固醇的水平，因此可能代表了血脂异常和心血管疾病的新治疗靶标。