抑郁症是严重影响全球公共健康的重大精神疾病，我国抑郁症患者约有5775万。最新研究表明，微生物在肠道中的作用可显著导致机体出现抑郁样行为，与抑郁症发病高度相关。基于项目组前期研究结果“人源化”抑郁小鼠粪便、血清和脑组织存在能量代谢紊乱；大量临床和动物代谢组学研究结果提示抑郁症的发生发展与能量代谢紊乱相关；且Hippo信号通路参与葡萄糖介导的能量代谢解过程，我们推测肠道微生物作用可能通过影响大脑葡萄糖与能量代谢，抑制Hippo信号通路活性，导致大脑情感认知功能损害。本项目以“肠道微生物—海马能量代谢—Hippo/YAP通路—抑郁表型及机制”为研究主线，结合生物化学、翻译后修饰组学、转基因动物模型和神经电生理等技术，解析能量代谢及Hippo通路在肠道微生物紊乱导致抑郁样行为中的功能及作用机制，以期发现肠道微生物影响中枢诱导抑郁的新作用机制，为抑郁症的治疗和药物作用新型靶点研发提供理论基础。

Major depressive disorder (MDD) is a serious mental illness that affects public health worldwide. There are about fifty seven million people suffering from MDD in China at present. Recent studies demonstrated that dysbiosis of the gut microbiome might have a causal role in the development of depressive-like behavior. Our previous work found a perturbed energy metabolic pathway in recipient depressed mice, and similar changes were found in depressed patients and animals either. Meanwhile, glucose-mediated energy homeostasis is an upstream event involved in regulation of the Hippo pathway. We speculate that gut microbiome may cause emotional and cognition dysfunction by affecting the energy metabolism and the Hippo pathway activity in hippocampus. In our work, we will try to explore and explain the roles of energy metabolism and Hippo pathway in germ free and gut microbiome remodeling depressive-like mice by biochemistry, post translational modification, transgenic animal models and neurophysiological methods. We aim at discovering a new mechanism of gut microbiome on brain and depressive-like behaviors, which will help provide new targets for the treatment in MDD.