肝纤维化是多种慢性肝病发展过程中所共有的阶段，可发展为肝硬化、肝癌。肠道微生物及其代谢物与肝纤维化进程密切相关。脱硫弧菌是硫酸盐还原菌在肠道内的重要成员，与肠道炎症等疾病密切相关。我们前期研究发现肝硬化病人及CCl4诱导的肝纤维化小鼠粪便中脱硫弧菌含量均显著升高；脱硫弧菌标准菌株（ATCC29577）及富集脱硫弧菌组分灌胃正常小鼠均使其肝脏纤维化；而灭活菌液无此现象。本课题拟在前期工作的研究基础上，通过体外肠上皮细胞、肝星状细胞、巨噬细胞及体内抗生素限制小鼠、无菌小鼠等模型，利用脱硫弧菌-细胞共培养、粪菌移植、代谢分析及转录组测序等技术，深入研究过度增殖的脱硫弧菌经肠肝轴及硫化氢相关信号分子导致肝纤维化的作用机制，并研究能否通过靶向脱硫弧菌或其代谢产物、或阻断其下游信号通路缓解肝纤维化进展。该研究结果将为慢性肝病临床转化研究提供新的诊断靶标与治疗靶点。

Liver fibrosis is a common stage in the development of various chronic liver diseases, which can lead to cirrhosis and liver cancer. Gut microbiota and their metabolites are closely related to the process of liver fibrosis. Desulfovibrio is one of the important members of sulfate-reducing bacteria in the body and is closely related to diseases such as intestinal inflammation. Our preliminary studies indicate that Desulfovibrio desulfuricans in the feces of patients with liver cirrhosis and mouse with CCl4-induced liver fibrosis was significantly increased; the type strain of D.desulfuricans (ATCC29577) and the enriched Desulfovibrio were administered to normal mice, and both lead to liver fibrosis; this phenomenon was not observed in inactivated ATCC29577. In this study, we will use the in vitro intestinal epithelial cells, hepatic stellate cells, macrophages and in vivo antibiotic-restricted mice, germ-free mice, and use the co-culture of D. desulfuricans and cells, fecal microbiota transplantation, metabolic analysis and transcriptome sequencing technologies to investigate the liver fibrosis caused by the overgrowth of D. desulfuricans through the liver-gut axis and hydrogen sulfide-related signaling. Further, we are going to study whether the liver fibrosis progression can be alleviated by targeting D. desulfuricans or its metabolites or blocking its downstream signaling pathway. Eventually this approach might lead to new therapeutic targets and therapies for patients with chronic liver disease.