肠毒性大肠杆菌（ETEC） 是一种威胁人类健康的肠道致病菌，感染后肠上皮黏膜免疫过度应答与肠损伤密切相关。多项研究显示罗伊氏乳杆菌具有肠道上皮损伤的修复功能但机制尚未全面阐明。最新研究发现罗伊氏菌色氨酸代谢产物吲哚3乳酸可诱导肠道独有的CD4+CD8αα+T细胞分化，具有重要的免疫调节功能。本团队前期发现ETEC患者病程与粪便中罗伊氏菌丰度相关；动物试验中低色氨酸膳食降可低罗伊氏菌移植对ETEC感染小鼠肠上皮细胞凋亡的保护作用，同时p38磷酸化水平和TNFα表达上调。据此提出如下假设：罗伊氏菌色氨酸代谢物可能调节CD4+CD8αα+T细胞分化，通过MAPK信号通路改善ETEC感染肠上皮损伤。本研究将利用免疫学等有关技术探讨罗伊氏菌色氨酸代谢物在调节肠道免疫细胞分化、MAPK通路激活以及对肠道功能的影响，揭示罗伊氏菌对ETEC感染保护作用的分子机制与影响因素，为益生菌的合理利用提供理论基础。

Enterotoxic Escherichia coli (ETEC) is a kind of intestinal pathogen that threatens human health. Intestinal injury is closely related to intestinal mucosal immune overreaction after ETEC infection. Many studies have shown that Lactobacillus reuteri has the repair function for intestinal epithelial injury, but the mechanism has not been fully elucidated. Most recent studies have found that indole-3-lactic acid, a L-tryptophan metabolite of Lactobacillus reuteri, can induce intestinal CD4+CD8αα+T cells differentiate and has important immunoregulatory functions. Previously, our research team found that the course of ETEC infection was related to the abundance of Lactobacillus reuteri in patients’ feces; furthermore, in animal experiments, low tryptophan diet decreased the protective effect of Lactobacillus reuteri transplantation on intestinal epithelial cell apoptosis caused by ETEC in germ free mice, while the phosphorylation level of p38 and the expression of TNF-α were up-regulated. The following hypothesis was put forward based on the previous results: Tryptophan metabolites of Lactobacillus reuteri may regulate the differentiation of CD4 + CD8αα+ T cells and improve the intestinal epithelial damage caused by ETEC infection through the MAPK signaling pathway. In this study, immunological techniques will be used to explore the role of Tryptophan metabolites of Lactobacillus reuteri in regulating intestinal immune cell differentiation, activation of MAPK pathway and its effect on intestinal function, revealing the molecular mechanism and influencing factors of Lactobacillus reuteri’s protective effect on ETEC infection, and providing basis for adjuvant treatment of ETEC infection.