前期完成的2项国家自然科学基金项目从代谢网络调控和肠吸收研究了经典方柴胡疏肝散水煎剂抗抑郁作用及配伍规律，并提示肠道菌群可能在柴胡疏肝散抗抑郁作用中扮演了重要角色。本课题拟首先应用16S rRNA分析结合代谢组学技术，考察肠道菌群结构及代谢产物的变化，研究复方对宿主和肠道菌群的调控作用；同时，应用LC-MS/MS 技术，考察宿主在抑郁及肠道菌群抑制状态下口服复方后吸收进入胃肠道、血浆及脑脊液中的化学成分差异，研究肠道菌群对宿主生物屏障及复方成分吸收代谢的作用。最后，借助生物信息学和数据挖掘技术，从抑郁大鼠肠道菌群多样性、代谢调控及机体对药物的处置分析宿主-肠道菌群-药物的相关性，阐述肠道菌群在复方抗抑郁作用中发挥的作用，从肠道菌群与“肠-脑”轴的相互作用，阐明其抗抑郁作用机制和药效成分，建立符合中医药理论和中药复杂体系的科学研究方法和思路，推动我国具有自主知识产权创新药研制和中药现代化。

Our previous NSFC projects have investigated the therapeutic mechanism of a water extract of Chaihu-Shu-Gan-San (CSGS) against depression and the compatible regularity based on regulation of metabolic network and the intestinal absorption properties. Our findings also suggest that gut microbiota should play a key role in the regulation of CSGS against depression. Thus, this project will focus on the correlation between gut microbiota and depression, and the role of gut microbiota on antidepressive effect of CSGS through 16S rRNA analysis and metabolomics. Meanwhile, the difference of ingredients distributed in gastrointestinal tract, plasma and cerebrospinal fluid (CSF ) after oral administration of CSGS extract in depression or inhibition of gut microbiota, will be investigated using LC-MS/MS technology. The results are expected to understand the influence of gut microbiota on permeability of gut tract and blood-brain barrier, and also beneficial to know the effects of gut microbiota on absorption and metabolism of CSGS. To explore the role of gut microbiota on the antidepressant effect of CSGS based on the altered gut microbiota and its impact on host metabolism, correlation analysis of the results from 16S rRNA analysis, metabolomics and drug disposition will be carried out by combining bioinformatics and data mining technology.The results will not only clarify the effective component of CSGS and its mechanisms of action against depression based microbiota–gut–brain axis, but also provide a novel ideal and approach suitable for exploring what and how the active constituents in complex system of TCMs generate the magic efficacy according to TCM theory.