唾液乳杆菌及其代谢产物在类风湿性关节炎中的作用机制

Gut microbiota and human immune system are closely related and tightly modulated by each other, and microbial metabolites may act as an important bridge in this interaction network. Increasing evidences have suggested that gut dysbiosis may play a critical role in the pathogenesis of rheumatoid arthritis. In this study, based on the early research of Lactobacillus salivarius strains which were identified and separated from patients with rheumatoid arthritis (Nat Med 2015), we systemically analyze and compare the full genomes and secondary metabolism product gene clusters of these strains. By using synthetic biology and microbial genetic engineering, we aim to edit the unique gene clusters essential for the synthesis of special metabolites. By using collagen induced arthritis small rat for model, we hope to address the mechanisms of immune system regulation in the pathogenesis of rheumatoid arthritis by Lactobacillus salivarius and its metabolites. This study will provide a new thought for RA treatment by using intestinal bacteria.

肠道菌群与人体免疫系统密切关联又相互调控，而肠道菌群代谢产物可能是二者进行“对话”的重要“桥梁”。越来越多证据提示肠道菌群紊乱可能在类风湿性关节炎(RA)的病理生理机制中具有重要调控作用。本项目将对课题组前期从RA患者鉴定分离出的异常表达的唾液乳杆菌(Nat Med 2015），进行全基因组比对分析和次级代谢产物基因簇预测分析，利用合成生物学、微生物遗传学工程对特定菌株代谢产物基因簇进行基因编辑，以胶原诱导关节炎小鼠为模型，明确唾液乳杆菌基因组及其代谢产物参与RA的免疫调控机制，为靶向利用肠道菌群治疗RA提供新的思路。