人体肠道、肠道微生物组与机体免疫系统形成一个复杂的有机整体。肠道微生物与宿主肠壁免疫功能细胞相互作用，影响机体的免疫机能，在自身免疫系统疾病的发生发展过程中起着重要作用。本项目以肠道真菌 (分节丝状菌，SFB)可促自身免疫性疾病的发生、发展为切入点，通过“PCR-DGGE指纹图谱技术初步了解RA患者及健康人的肠道真菌分子生态结构特征”、“PacBio RS 高通量测序平台建立早期RA患者及健康人的肠道真菌18S rDNA 全长数据库”、 “Mothur 及R等生物信息学软件探寻早期RA区别于健康人的真菌 ‘亚肠型’结构”、“qPCR验证这些差异性真菌”、“检索文献资料，从真菌的生物学特性，解析其在RA发生、发展过程中的可能作用机制”五步法揭示RA患者肠道真菌分子生态结构特征，并找出与RA发生、发展密切相关的真菌，初步筛出潜在的可用于RA高危人群预警监测的肠道真菌标志物。

The gut, intestinal microbiome and immune system form a complex integrated structure，in which intestinal microbiome interplays with immune cells in the intestine, and influences the human immune system function. Thus, intestinal microbiome plays a critical role in the development of autoimmunity disease including rheumatoid arthritis (RA). Intestinal microbial structure and function can reflect human susceptibility to the disease, suggesting that intestinal microbiota possess a potential monitoring and diagnostic function. It is significantly scientific and frontier to search for intestinal microbial markers monitoring early RA. In this study, based on the breakthrough point that intestinal fungi（segmented filamentous bacteria, SFBs）promote the progression of RA, we establish intestinal fungal 18S rDNA full sequences database of patients with early RA by PacBio RS high-throughput sequencing. And then we want to find out the non-invasive, effective and frontier intestinal fungal markers to monitor the early RA through the following five steps: “To see the characteristics of intestinal fungal composition in RA patients which are different from controls using Denaturing gradient gel electrophoresis (DGGE) fingerprinting technology”, “To build the human intestinal fungi database of the whole length of the 18S rDNA sequence using PacBio RS high-throughput sequencing technology”, “To understand the key fungi sub-enterotypes between RA patients and healthy individuals by the Mothur and R software”, “To verify and validate the key fungi in the independent more samples among RA patients and healthy individuals by the RT-PCR methods” and “To understand the effects and possible mechanism of the key fungi involved in the development of RA disease by reference”. These studies and findings are greatly significant for the early monitoring, early prevention and early diagnosis and treatment of RA.