艰难梭菌感染(CDI)是院内感染性腹泻及肠炎的重要病因之一，肠道菌群紊乱与其发生密切相关。我们前期发现CDI患者肠道菌群种类和代谢改变，产丁酸厌氧菌比例明显降低，其中以毛螺菌科R.intestinalis 降低最显著，其可能为CDI发生发展中的潜在关键功能菌。课题组预实验也发现R.intestinalis具有潜在肠道黏膜保护功能，但作用机制不明。课题组拟构建R.intestinalis 干预小鼠艰难梭菌感染动物模型，从肠道菌群、炎症指标、肠道黏膜屏障等方面观察其肠道黏膜保护作用，并正、反向调控Caco-2细胞上NOD1的表达，探明R.intestinalis对NOD1表达关键调控因子的影响，观察相关信号转导通路蛋白活化情况及下游炎症因子表达差异，明确其对肠道黏膜保护作用的分子机制，进而揭示在CDI发生发展中的作用，为今后开发R.intestinalis为肠道益生菌防治CDI提供理论依据。

Clostridium difficile infections (CDI) is considered to be the main cause of bacterial infectious diarrhea in nosocomial setting and the dysbiosis of intestinal microbiota is strongly associated with CDI. We found some alterations of species and metabolisms of the human intestinal flora early in CDI patients. Butyrate-producing anaerobic bacteria, especially R.intestinalis from Lachnospiraceae family are significantly depleted, which may play vital roles in the developemt of CDI. Our previous preliminary study also shows that R.intestinalis has the potential protective effects for the intestinal barrier, while the mechanisms remain unclear. In this project, we aim to explore the protective effects from the intestinal microbial composition, intestinal inflammation, intestinal physical barrier and immune barrier in a mouse model of CDI. And we also try to understand the role of R.intestinalis on the expression of the NOD1 key regulatory factor by up-regulating and down-regulating the expression of NOD1 in Caco-2 cells. Meanwhile, we also explore the changes of key protein in the NOD1 related signaling transduction pathways, and the expression of inflammatory cytokines. According to our present study, we will understand the specifc mechanisms of R.intestinalis in the intestinal mucosal protection in a deeper level, which will reveal the role of R.intestinalis in the development of CDI and provide a theoretical basis for R.intestinalis to be developed into probiotics.