Ma Xin, Li Meng, Zhang Yuanyuan, Xu Tingting, Zhou Xinchen, Qian Mengqi, Yang Zhiren, Han Xinyan
Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China.
Hainan Institute of Zhejiang University, Yongyou Industry Park, Yazhou Bay Sci-Tech City, Sanya, China.
Elife. 2025 Feb 6;12:RP92906. doi: 10.7554/eLife.92906.
As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. () and () were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that and relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of was better than . We, therefore, identified whether protected against ETEC infection using basal-out and apical-out intestinal organoid models. did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. ila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway.
作为最大的黏膜表面,肠道构建了物理、化学、微生物和免疫屏障以保护机体免受病原体侵袭。肠道微生物群的紊乱会加剧病原菌的侵袭和肠道屏障损伤。粪便微生物群移植(FMT)是治疗微生物群相关疾病的一种有前景的方法,其中有益菌株的植入是影响FMT疗效的一个重要因素。本研究的目的是探讨FMT对感染产肠毒素大肠杆菌(ETEC)的抗生素诱导的微生物群紊乱(AIMD)模型的影响。我们使用仔猪、小鼠和肠道类器官模型来探讨FMT对ETEC感染的保护作用及机制。结果表明,FMT可调节肠道微生物群,并增强AIMD仔猪对ETEC K88攻击的保护作用,表现为肠道病原菌定植减少和肠道屏障损伤减轻。()和()被鉴定为可能在FMT中起关键作用的两种菌株。我们进一步研究了这两种菌株对AIMD小鼠模型中ETEC感染的缓解作用,结果显示()和()通过维持Treg/Th17细胞比例缓解ETEC诱导的肠道炎症,并通过适度激活Wnt/β-连环蛋白信号通路减轻上皮损伤,而()的效果优于()。因此,我们使用基底外侧和顶端外侧肠道类器官模型确定()是否对ETEC感染具有保护作用。()确实能保护肠道干细胞并刺激肠道上皮细胞的增殖和分化,并且()的保护作用被Wnt抑制剂逆转。FMT减轻了AIMD模型中ETEC诱导的肠道屏障损伤和肠道炎症。ila被鉴定为FMT中通过介导Wnt/β-连环蛋白信号通路促进肠道干细胞增殖和分化的关键菌株。