肠道菌群来源的外膜囊泡调控Treg/Th17平衡参与子痫前期发病的作用机制研究

子痫前期（PE）严重危及母胎安全，免疫失衡是其重要发病机制。课题组前期研究发现PE患者肠道菌群紊乱，小鼠移植PE粪菌后出现血压升高等PE样症状，并伴Treg/Th17失衡，提示肠道菌群失调参与PE发病，免疫失衡是其中重要环节，但具体作用机制未见报道。已知外膜囊泡（OMVs）是细菌向外界传递分子效应的主要媒介，前期实验发现PE肠菌来源的OMVs可激活初始CD4+T细胞PI3K/Akt/mTOR信号通路，继而影响Treg/Th17平衡。据此假设，肠道菌群来源的OMVs介导Treg/Th17免疫失衡从而诱发PE。本研究拟从肠道微生物视角出发，以肠道菌群及其分泌的OMVs为切入点，在人体、动物、细胞三个层次，通过宏基组、蛋白组等高通量测序及粪菌移植、囊泡注射等技术方法，深入探讨肠道菌群失调参与PE发病的具体分子机制，可为PE发病机制的研究开辟新思路，并为以肠道菌群为靶标的PE防治策略提供新依据。

Preeclampsia (PE) seriously endangers the safety of mothers and fetuses of which the key pathogenesis is immune imbalance. Previous research of our team has shown dysbiosis of gut microbiome in PE patients and that fecal microbiota transplantation from PE patients to mice models causes imbalance of Treg/Th17 cells accompanied by PE-like symptoms like increasing blood pressure. All of these suggest the involvement of gut microbiome in PE where immune imbalance plays a key role. However, the specific mechanism has not been reported yet. Outer membrane vesicles (OMVs) are known to be the main mediators of bacteria transmitting molecular to the outside world. Pre-test has shown that OMVs derived from gut flora of PE patients could impact the balance of Treg/Th17 cells by activating PI3K/Akt/mTOR signaling pathway in naive CD4+ T cells, according to which we hypothesized that gut microbiome-derived OMVs regulates Treg/Th17 balance in the pathogenesis of PE. Therefore, in this study, we intend to take the gut microbiome and its OMVs as an entry point so as to further explore the specific mechanism of gut microbiome-derived OMVs in PE at human, animal and molecular levels by using high-throughput sequencing such as metagenome, proteome, metabolome, as well as other techniques include fecal transplantation, vesicle injection. The present study could shed light on the novel mechanism of etiology in PE from the perspective of gut microbiome and provide brand-new ideas in prevention and treating strategies of PE in the future.