基于C1orf106/ CYTH-1/AFR6通路的IBS-D和UC湿热证与肠道菌群相关性及清热利湿经典方剂干预机制研究

溃疡性结肠炎（UC）和腹泻型肠易激综合征（IBS-D）严重影响患者的生活质量，临床上针对常见湿热证采用清热利湿法疗效显著。肠道菌群失调与UC和IBS-D的免疫紊乱、肠黏膜屏障损伤密切相关，肠道微环境变化导致 C1orf106/ CYTH-1/AFR6通路异常致肠黏膜屏障损伤，可能是UC和IBS-D湿热证共同的发病机制。本课题基于临床，研究清热利湿复方调节肠道菌群、修复肠黏膜屏障、重建肠道微环境的作用及机制。研究采用宏基因组学和代谢组学相结合的方法，通过对比健康人、IBS-D湿热证、UC湿热证患者之间肠道菌群及其与宿主共代谢产物的差异，探寻湿热证与肠道菌群及其与宿主共代谢产物的关联性，实验研究基于C1orf106/ CYTH-1/AFR6通路进一步明确清热利湿复方的作用靶点。本研究通过对UC及IBS-D湿热证与肠道菌群之间的关联性的研究，对揭示中医理论异病同治的内涵具有重要的学术意义。

Ulcerative colitis(UC) and diarrhea-predominant irritable bowel syndrome(IBS-D) seriously affect the quality of life in patients. Clinically, it is effective to apply therapeutic method of clearing heat and promoting diuresis to the common syndrome of dampness-heat. Dysbiosis of intestinal microbiota is closely related to the immune imbalance and intestinal mucosal barrier injury. C1orf106/ CYTH-1/AFR6 signal pathway, which derive from intestinal microenvironment changes, is the mainly cause of intestinal mucosal barrier injury, and this is may be the common pathogenesis of dampness-heat syndrome in UC and IBS-D. Based on the clinic, the project is to study the effect and mechanism of Chinese compound formula of clearing heat and promoting dieresis in modulating intestinal microbiota dysbiosis, repairing intestinal mucosal barrier and reconstructing intestinal microenvironment. With the combination of metagenomics and metabonomics, the study compare the differences of co-metabolites of intestinal microbiota and host within the healthy people, IBS-D patients with dampness-heat syndrome and UC patients with dampness-heat syndrome, to explore the relevance between intestinal flora and host co-metabolites. Furthermore, the experimental study is to clarify the drug targets via C1orf106/ CYTH-1/AFR6 signal pathway. Through the study of association between dampness-heat syndrome in UC and IBS-D patients and intestinal microbiota, it is of important academic significance to reveal the Chinese theory intension of “homotherapy for heteropathy”.