肝硬化患者TIPS术后肝性脑病（HE）发生率明显增加，一旦发生HE死亡风险高达50%，但HE的发生机制尚未完全阐明。近年来，肠道菌群介导的胆汁酸代谢异常在HE发生中的作用逐渐得到证实。我们的研究表明TIPS术后HE患者粪便明串珠菌科和奈瑟氏菌科丰度升高，且伴有血清胆汁酸水平升高。既往研究表明胆汁酸可通过调控法尼醇X受体（FXR）和顶端钠依赖性胆盐转运体（ASBT）介导中枢神经系统功能。我们发现，肝硬化小鼠回肠末端FXR表达降低，ASBT表达升高，部分小鼠存在空间记忆受损。上述结果提示，胆汁酸异常有可能通过调控FXR/ABST促进HE的发生。因此本项目拟通过粪菌移植、胆汁酸干预、行为学检测等方式，系统研究肠道菌群调控胆汁酸代谢介导FXR/ABST在TIPS术后肝性脑病发生中的作用机制。本项目研究结果不仅有助于揭示肠道菌群在HE发生中的作用机制，并且可以为探索肝硬化HE全新治疗方法提供思路。

The incidence of hepatic encephalopathy (HE) is further increased after TIPS for patients with liver cirrhosis, which was associated with a mortality of more than 50%. The pathophysiology of HE is incompletely understood. Recently, the role of gut microbiome-mediated bile acid (BA) metabolism dysregulation in the occurrence of HE has been demonstrated. Our study shows that the abundances of Leuconostocaceae and Neisseriaceae were increased, and the serum BA levels were also increased for patients with HE after TIPS. Certain BA can influence central nervous system function through farnesoid X receptor (FXR) and apical sodium-dependent bile salt transporter (ASBT). We found that the expression of FXR at the end of the ileum in cirrhotic mice decreased, the expression of ASBT increased, and some mice had impaired spatial memory. The above results suggest that BA may promote the occurrence of HE by regulating FXR/ABST. Therefore, the present project aims to investigate the mechanisms of gut microbiome-mediated bile acid metabolism dysregulation in the occurrence of HE after TIPS in liver cirrhosis via FXR/ABST through fecal microbiota transplantation, BA intervention, and behavioral testing, etc. Our project can not only clarify the mechanism of gut microbiota dysbiosis in the occurrence of HE in liver cirrhosis, but also can provide a new therapeutic target for the treatment of HE.