基于肠道菌群/SCFAs/FFA2途径探讨路氏润燥汤调节Th17/Treg免疫平衡治疗干燥综合征的机制

干燥综合征（SS）是一种慢性自身免疫性疾病，目前无特效治疗方法。临床研究证实路氏润燥汤治疗SS疗效显著，前期动物实验表明其可降低IL-17、TNF-α等水平，具有良好的抗炎、免疫调节作用。我们通过宏基因组学测序发现，SS患者肠道菌群较健康人多样性降低，产生丁酸的菌属明显下降，推测SS的免疫失调可能与SCFAs的异常减少密切相关。肠道菌群失调及其代谢物异常会导致Th17/Treg免疫失衡，Th17/Treg免疫失衡在SS的发病中发挥重要作用。我们推测路氏润燥汤可能通过调节肠道菌群平衡及代谢物分泌，恢复Th17/Treg免疫平衡而发挥作用。本项目拟通过临床和动物实验研究，在路氏润燥汤的干预下，利用宏基因组学、代谢组学及关联分析对SS患者和NOD鼠肠道菌群、代谢物表达进行对比、分析，并采用相应方法对相关因子、组织病理进行检测，从肠道菌群/SCFAs/FFA2阐释路氏润燥汤治疗SS的机制。

Sjogren's syndrome (SS) is a chronic autoimmune disease,there is currently no particularly effective treatment. Early clinical studies confirmed that Lushi Runzao decoction has a significant effect on SS. Animal experiments showed that it can reduce the levels of IL-17 and TNF - α, and has good anti-inflammatory and immunomodulatory effects.We found that the diversity of intestinal flora of SS patients was lower than that of healthy people, and the bacteria producing butyric acid was significantly decreased. We speculated that the immune disorder of SS might be closely related to the abnormal reduction of SCFAs. The imbalance of intestinal flora and its metabolites will lead to the imbalance of Th17 / Treg immunity, which plays an important role in the pathogenesis of SS. We speculate that Lushi Runzao Decoction might play an important role in restoring Th17 / Treg immune balance by regulating intestinal flora balance and metabolite secretion. In this project, We will use Lushi Runzao Decoction,through clinical and animal experimental research, compare and analyze the expression of intestinal microflora and metabolites in SS patients and NOD mice tested by macrogenomics,metabonomics and correlation analysis, and the relevant factors and histopathology will be detected by corresponding methods, and we will try to discuss the mechanism of Lushi Runzao Decoction in treating SS through intestinal microflora /SCFA / FFA2.