证候生物学基础是中医有待突破的关键科学问题之一。本课题基于非酒精性脂肪肝（NAFLD）肠道微生态研究的国内外进展，结合课题组前期对慢性肝病湿热证肠道菌群变化的研究及清热化湿中药对实验性NAFLD肠道菌群具调节作用的结果，提出“肠道微生态变化是湿热证的重要病理基础，非酒精性脂肪肝湿热证在肠道菌群－肠黏膜免疫－肝脏病变的病理途径中具特征性改变”的假说。拟运用多组学融合技术（宏基因组、宏转录组、代谢组等）及生物信息分析技术等开展论证：①以异病和异证为对照，开展NAFLD湿热证患者与肠道微生态相关性的横断面研究；②以清热化湿方药为干预手段，进行NAFLD患者湿热证与肠道菌群相关性的干预性验证；③基于“肠道菌群-肠黏膜免疫－肝脏病变”和方药干预，运用NAFLD模型及悉生动物菌群移植模型，开展肠道微生态与相关方剂治疗作用的相互影响和机制研究。本研究可为湿热证的肠道微生态变化的生物学基础提供科学依据。

It is important to discover the biological basis of syndromes in traditional Chinese medicine. Based on the pathogenesis advance of non-alcoholic fatty liver disease (NAFLD), the correlation between the damp-heat syndrome and chronic liver diseases we found previously and the effects of Chinese medicine for clearance of heat and dampness on the intestinal flora in experimental NAFLD, it is proposed that “intestinal microecology disorder is the important pathological basis of the damp-heat syndrome and the pathological changes in intestinal microflora, mucosal immunity and liver are the features of the damp-heat syndrome in NAFLD. In the present study, the technologies and analysis methods of metagenomics, metatranscriptome, metabonomics and bioinformatics are employed and the research plans are described as follow: ①to carry out cross-sectional studies on the correlation between the intestinal microflora and the damp-heat syndrome in NAFLD patients controlled by other diseases and syndromes respectively; ② to verify the correlation between intestinal flora and the damp-heat syndrome in NAFLD patients by treatment with Chinese medicine for clearance of heat and dampness; ③ to investigate the mechanisms of Chinese medicine for clearance of heat and dampness action on the intestinal microflora in NAFLD by using NAFLD animal models and gnotobiotic animals. It is expected to provide the scientific evidence for the biological basis of gut microecology disorder in the damp-heat syndrome by the proposed project.