中药皂苷类成分经肠道菌群脱糖基代谢与其药效发挥密切相关，肠道菌群失调可能引起中药皂苷类成分胃肠道代谢处置改变，进而影响其药效发挥。本项目拟以人参总皂苷为模型药，在慢性束缚性应激和抗生素诱导的肠道菌群失调模型大鼠上，基于LC-Q-TOF/MS同时定性定量技术，系统表征人参总皂苷在菌群失调下的体内代谢转化和尿、粪排泄差异，并探讨微生态制剂干预菌群失调后人参皂总皂苷的体内代谢处置转归；从各肠段糖苷酶活性、紧密连接蛋白和P-gp等外排转运体的角度，深入研究引起人参总皂苷胃肠道代谢处置差异的可能机制；此外，应用PCR-DGGE、实时定量PCR等技术研究肠道菌群失调下的菌群结构谱变化，将其与糖苷酶活性相关联。本项目在为诠释肠道菌群失调对人参总皂苷代谢处置及其作用机制的同时，还为其他皂苷类成分在肠道菌群失调下体内代谢处置差异机制提供共性研究思路与方法。

Gut microbita mediated deglycosylation of most saponins from Chinese medicine is a critical step for achieving their pharmacological effects. Thus, we hypothesized that gut microbiota dysbiosis may influence the pharmacokinetics, metabolism and disposition of the saponins, ultimately affecting their pharmacological efficacy. In this project，total ginsenoside were selected as the model drug and rat model of microbiota dysbiosis induced by chronic restrain stress and treatment of antibiotics was applied. Firstly, the pharmacokinetics, urine and fecel excretion profiles of the ginsenoside and its metabolites were simultaneously studied using a qualitative and quantitative method based on LC-Q-TOF/MS. The intervention effects of the probiotcs on the metabolism and disposition of ginsenosides in gut microbiota dysbiosis rat were also studied. The glycosidase activity, the epression of tight junction protein (ZO-1, Occludin) and the efflux transporter like P-gp were also investigated to illustrate the potential mechanisms involved in the pharmacokinetic difference of gisenosides between the normal and dysbiotic rat. Finally, the DGGE-PCR and Real time-PCR technique were applied to study the structural shift of the gut microbiota and establish the correlation between the composition of gut microbiota and the glycosidase activity. Our result may provide a novel and general strategy for studying the effcts of gut microbiota dysbiosis on the pharmacokinetics profiles of total ginsenosides and other saponins.