Akkermansia muciniphila新菌株与乳酸杆菌协同调控吲哚-3-乙酸在治疗抗生素相关性肠炎中的机制

粪菌移植（FMT）是治疗抗生素相关性肠炎的重要手段，但因其美学、难以量产等不足，寻找新型益生菌或部分替代FMT的配方菌群移植已成热点。本项目前期发现FMT治疗有效的患者粪中Akkermansia muciniphila（A. muciniphila）增加、尿蛋白组学示Nrf2蛋白增加、尿磁共振氢谱示吲哚衍生物增加；从FMT健康供体中分离出4株中国人源A. muciniphila菌，并证实其与乳酸杆菌共培养能增加吲哚-3-乙酸（IAA）生成。遂假设：A. muciniphila新菌株能与乳酸杆菌共作用，增强IAA代谢，介导Nrf2抗氧化应激。拟通过动物模型、肠类器官、慢病毒转染、多组学等技术，研究中国人源A. muciniphila菌株与乳酸杆菌共代谢IAA并活化Nrf2通路在治疗抗生素相关性肠炎中的机制，为配方菌群移植奠定理论基础。

Fecal microbiota transplantation (FMT) is an important strategy for the treatment of antibiotic associated colitis (AAC). However, due to its aesthetics limitation and the difficulty of mass production, it is a hot field in searching for new probiotics and synthetic microbiota to partially replace FMT. In our previous study, a new type of probiotics Akkermansia muciniphila (A. muciniphila), urinary Nrf2 protein and indole derivatives were found to be significantly increased in patients who achieved significant clinical efficacy from FMT. We isolated 4 Chinese A. muciniphila strains from FMT healthy donors and confirmed their ability to metabolize indole-3-acetic acid (IAA). In addition, the co-culture of A. muciniphila and Lactobacillus could increase IAA metabolism, but there exist differences among different strains. We therefore proposed the hypothesis: the new strain of A. muciniphila could co-act with Lactobacilli to enhance the production of IAA, which could act on the nuclear factor E2related factor 2 (Nrf2) antioxidant stress signaling pathway. This study will aim to investigate the combined effects and anti-inflammation mechanism of A. muciniphila and Lactobacilli co-metabolizing IAA to act on Nrf2 pathway based on researches of animal models, intestinal epithelial organoid, lentivirus vector and multi-omics. It would provide an important theoretical evidence for the clinical application of synthetic microbiota transplantation.