肠道菌群产生多种代谢产物参与宿主代谢，然而宿主调控肠道菌群的机制至今尚不明确。肠缺氧诱导因子2α(HIF-2α)在肥胖的发生中发挥重要作用。肠道菌群可以通过调节肠HIF-2α影响铁离子吸收，参与宿主代谢。然而，肠HIF-2α是否能够调节肠道菌群尚不清楚。我们的预实验结果显示：肠HIF-2α敲除可以降低乳酸含量，抑制普通拟杆菌生长，升高胆汁酸DCA和TCA水平，促进白色脂肪米色化。G蛋白偶联胆汁酸受体TGR5是重要的胆汁酸膜受体。既往研究表明，白色脂肪TGR5激活能诱导白色脂肪米色化。由此我们提出假说：肠HIF-2α通过普通拟杆菌-胆汁酸-脂肪TGR5代谢轴抑制白色脂肪米色化。本项目拟发现肠HIF-2α调控乳酸代谢影响普通拟杆菌的分子机制；探索肠道菌群-胆汁酸-脂肪TGR5轴在肠HIF-2α影响白色脂肪米色化中的作用，为防治肥胖及相关代谢疾病提供理论依据。

The gut microbiota regulate host metabolic process via multiple metabolites, however, it’s unclear that how host gene modulate the composition of gut microbiota. Intestinal hypoxia-inducible factor-2α (HIF-2α) plays the crucial role in the pathogenetic process of obesity. It has reported that the gut microbiota produce several metabolites, which suppress HIF-2α, resulting in decreased intestinal iron absorption. However, how intestinal HIF-2α influences gut microbiota remains unclear. Our preliminary results show that, intestine-specific HIF-2α ablation decreased lactate levels and led to a reduction in Bacteroides vulgatus level and elevation in TCA and DCA levels, which promotes the beiging of white adipose tissue. TGR5, an important membrane receptor of bile acids in white adipocytes, has proven to provoke white adipose tissue beiging remarkably. From the above, we assume that intestinal HIF-2α mediates white adipose tissue beiging through the Bacteroides vulgatus-bile acids-adipocyte TGR5 axis. We aim to discover the molecular mechanism that how HIF-2α regulates lactate level and affects Bacteroides vulgatus, and further explore the role of B. vulgatus-bile acids-adipocyte TGR5 axis in the inhibition of intestinal HIF-2α on white adipose tissue beiging, providing novel targets for the treatment of obesity and related metabolic disorders.