大黄硝石汤（DHXSD）是《金匮要略》中治疗“黄疸”经典方剂。申请者前期发现DHXSD可有效防治大鼠胆汁淤积性肝损伤。虽然胆汁淤积性肝损伤的发生与发展与肠道菌群关系密切，但鲜有从肠道菌群角度来探讨DHXSD治疗胆汁淤积性肝损伤物质基础与作用机制。本课题拟以肠道微生态的“失调”与“平衡”为切入点，基于“肠-肝-肠道菌群”轴融合分子生物学和现代分析仪器代谢组学方法进行以下分析：（1）DHXSD体外及体内入血成分；（2）DHXSD成分经肠道菌群的代谢；（3）胆汁淤积性肝损伤模型大鼠造模前后及DHXSD干预前后的肠道菌群谱和代谢组学谱。最终筛选胆汁淤积性肝损伤 “代谢生物标志物”与“肠道生物标志菌属”，构建“DHXSD-肠道菌群-胆汁淤积性肝损伤”研究体系，挖掘其治疗胆汁淤积性肝损伤与肠道微生态“失调”、“平衡”之间的关系并阐释其物质基础及机制，并为研究中医药治疗与肠道菌群相关疾病提供新思路。

Da-Huang-Xiao-Shi decoction (DHXSD) is a classic prescription for the treatment of cholestatic liver injury in the synopsis of the Golden Chamber. Based on metabonomics, our group found that DHXSD can effectively prevent and treat cholestatic liver injury in rats. Although the occurrence and development of cholestatic liver injury is closely related to gut microbiota, there are few studies on the substance basis and mechanism of DHXSD in the treatment of cholestatic liver injury from the perspective of gut microbiota. This paper intends to take the: “imbalance” and “balance” of intestinal microecology as the starting point, based on the molecular biological techniques such as Gut-Liver-Microbiome axis combined with molecular biology and the metabonomics methods of modern analytical instruments to analyze the following: (1) the absorbed components of DHXSD in vitro and in vivo; (2) the metabolism of DHXSD components through gut microbiota; (3) The gut microbiota spectrum and metabonomic spectrum analysis before and after the model of cholestatic liver injury and the intervention of DHXSD. Finally, the metabolic biomarkers and gut microbiota biomarkers of cholestatic liver injury were screened and identified, and the research system of “DHXSD-gut microbiota-cholestatic liver injury” was constructed to explore the relationship between its treatment of cholestatic liver injury and intestinal microecological “imbalance” and “balance”. Ultimately interpretation its substance basis and mechanism of the treatment of cholestatic liver injury. It also provides a new concept for studying the mechanism of traditional Chinese medicine in the treatment of diseases related to gut microbiota.