基于肠道菌群中西医结合防治糖脂代谢性疾病的机制研究

中西医结合防治糖脂代谢性疾病已成为临床常用手段，肠道菌群在糖脂代谢中扮演重要角色，中药与肠道菌群相互作用共同调节机体糖脂代谢。本项目将肠道菌群与中医药整体调节理论相结合，以已经获得临床批件的三叶片为研究载体，采用临床基础相结合研究模式，选择糖尿病前期和糖尿病合并脂代谢紊乱受试者，集成“临床、微生物、中药代谢、分子生物、生物信息、中药药理”等多学科交叉方法和技术，围绕中药复方与肠道菌群相互作用调节糖脂代谢进行研究。确认三叶片调节糖脂的作用机制与肠道菌群因果关系，发现中药调控糖脂代谢关键菌群和化学物质基础；从能量代谢、氨基酸代谢及糖脂代谢等揭示调节糖脂代谢的生物标志物；探索中药防治糖脂代谢异常的"化学物质-肠道菌群-体内化学成分和代谢产物-作用器官组织-靶点信号通路"，阐明中西医结合防治糖脂代谢性疾病机制。为糖脂代谢异常疾病临床治疗提供科学依据，也为中药研发提供新依据、新靶点、新思路和新方法。

Combination of TCM and western medicine has become an effective method to prevent disorders of glycolipid metabolism. Gut microbiota plays a crucial role in glycolipid metabolism and can cross-talk with TCM. This project intends to guide gut microbiota research with the theory of TCM, integrating the clinical research with mechanistic study, using the clinical licensed Three Leaves tablets to treat diabetic patients in early stage and patients suffering diabetes and lipid metabolism disorder. We will integrate technologies from different scientific fields such as clinical research, microbiology, drug metabolism, molecular biology, bioinformatics, pharmacology etc. to study the how Chinese medicine regulates glycolipid metabolism through influencing gut microbiota. The goals of this project are：To determine the mechanism of Three Leaves tablets on regulating sugar and lipid metabolism and whether gut microbiota can mediate the effects of Three Leaves tablets；To identify the major active compounds in Three Leaves tablets which regulate glycolipid metabolism and bacteria that influence sugar and lipid metabolism; To identify biomarkers of sugar and lipid metabolism in energy, amino acid and carbohydrates metabolism pathways; To unveil the relationship of chemical ingredients, gut microbiota, compound metabolism, target organs/tissues and the drug targets/signaling pathways; To uncover the mechanism of the integrative medicine in treating metabolism disorder. This project will not only provide scientific evidence for the disease management but also shed light on developing modern Chinese medicine by providing new basis, new targets, new ideas and new methods for TCM research.