肠道菌群与胆汁酸代谢的相互作用参与艰难梭菌感染（CDI）的发生发展过程，但其作用机制尚不明确。我们的前期研究发现健康人肠道含量丰富的抗炎共生菌F. prausnitzii（Fp）在CDI儿童肠道中显著减少；粪菌移植（FMT）可显著增加CDI儿童肠道Fp的丰度和改善肠道胆汁酸代谢；Fp丰度的增加与FMT治疗CDI效果呈正相关。我们假说Fp可调节肠道胆汁酸代谢，恢复正常肠道菌群组成与肠道免疫平衡来治疗CDI。本项目将以抗生素暴露诱导的CDI小鼠模型来研究Fp对CDI的治疗作用；研究Fp对CDI小鼠胆汁酸代谢的影响，以及胆汁酸抑制CDI炎症的作用与机制；并通过法尼醇衍生物X受体（FXR）基因敲除小鼠探讨Fp调节胆汁酸代谢激活FXR信号通路治疗CDI的细胞分子机制，为揭示Fp在CDI发生发展中的重要作用提供理论依据，为开发可调节肠道菌群平衡和胆汁酸代谢治疗CDI的益生菌提供实验基础。

The interaction between gut microbiota and bile acid (BA) metabolism plays important role in the pathogenesis of Clostridium difficile infection (CDI), however, the mechanism is unclear. Our previous data showed that F. prausnitzii (Fp), an anti-inflammatory symbiotic bacteria riches in intestinal tract of healthy people, was decreased significantly in the intestinal tract of CDI children; fecal microbiota transplantation (FMT) could significantly increase the abundance of Fp in the intestinal tract of CDI children and improve the metabolism of bile acid; the increase of Fp abundance was positively correlated with the therapeutic effect of FMT on CDI. We hypothesize that Fp can regulate intestinal bile acid metabolism, restore normal gut microbiota composition, and intestinal immune balance to cure CDI. In this proposed study, we are going to study the therapeutic effect of Fp on CDI mice model induced by antibiotic exposure; the effect of Fp on bile acid metabolism and the mechanism of bile acid in inhibiting intestinal inflammation in CDI mice; and to investigate the molecular mechanism of Fp in regulating bile acid metabolism and curing CDI by FXR gene knockout mice. Our study will provide experimental evidences to reveal the roles of Fp in the pathogenesis of CDI, and suggest the potential application of symbiotic bacteria-based CDI treatment in the future.