肠道菌群与人体免疫系统密切关联又相互调控，而miRNA可能是二者进行“对话”的重要“桥梁”。越来越多的证据包括申请人前期研究(Nat Med 2015)均提示肠道菌群紊乱可能在自身免疫病(AIDs) 病理生理机制中具有重要的作用，申请人前期也发现和鉴定了一些miRNA在人类AIDs免疫致病中的调控作用(Sci Transl Med 2014)。本项目通过肠道宏基因组学及肠道miRNA表达分析，解析肠道菌群、机体miRNA紊乱及其调控机制与AIDs发生发展的关系。结合AIDs代表性疾病-系统性红斑狼疮(SLE)和类风湿关节炎(RA)的具体临床表现，在系统分析比对SLE/RA肠道菌群异常、miRNA调控和致病作用既共性又各自特异的机制基础上,筛选有效的诊断、疗效及预后判断分子分型标志物，构建新型敏感而特异的诊断模型，探索早期阻断疾病发生、发展的潜在治疗靶点。

Gut microbiota and human immune system are closely related and tightly modulated by each other, and miRNA may act as an important bridge in this interaction network. Increasing evidences, including ours (Nat Med 2015), have suggested that gut dysbiosis may play a critical role in the pathogenesis of autoimmune diseases(AIDs). We have also identified several miRNAs as potent immunomodulators which may promote the development of AIDs(Sci Transl Med 2014). In this study, we aim to investigate the relationship between microbiome distribution, miRNA dysregulation and the development of AIDs. To address this purpose, we choose systemic lupus erythematosus and rheumatoid arthritis as two representatives of AIDs, systemically analyzing and comparing the gut microbiota, miRNA dysregulation and correlating them with the clinical manifestations. This study will help to interpret both common and specific mechanisms of dysbiosis and miRNA dysregulation in AIDs, therefore develop promising biomarkers and build microbiome composition models for better diagnosis and prediction of treatment efficacy, and identify new target for the treatment of AIDs.