近年研究显示肥胖、2型糖尿病（Type 2 Diabetes Mellitus, T2DM）与肠道微生物改变密切相关。作为甜味剂广泛应用、药食兼用罗汉果具有抗糖尿病作用，且对正常人血糖无影响。基于T2DM与代谢、肠道菌群的密切关系，本课题在前期研究基础上，拟采用抗T2DM多层次药效评价体系，对罗汉果总皂苷进行分离和活性筛选；以代谢组学为手段，结合T2DM相关肠道菌群变化，考察活性组分群在正常和模型动物体内的吸收、分布、代谢、排泄）变化过程，及其对机体内源性成分的影响，阐明其在正常、模型动物中的作用差异，以及活性组分群与肠道菌群间相互关系；从外源性成分代谢、肠道菌群和内源性成分变化三个层面阐明其功效物质发挥抗糖尿病活性的作用机制。本课题的实施为药食兼用药材罗汉果抗T2DM的功效物质基础、作用机制和体内过程奠定基础；为从机体代谢角度研究和发现抗糖尿病的活性天然产物提供借鉴。

Mounting evidence indicates gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders. As a widely used non-nutritive sweetener, an edible Chinese medicinal material, Siraitiae Fructus was reported that the anti-diabetes activity on experimental animal, and no effect on normal human’s blood sugar concentration in clinic. Based on our previous studies, we aim to separate and screen the active compositions from total saponins of Siraitiae Fructus, used multilevel pharmacodynamics evaluation system of anti-T2DM. The strategy of metabolomics combined T2DM related microbiota was employed to compare investigate the absorption, distribution, metabolism and excretion of the active compositions in T2DM with obesity model and normal animal groups, and the influence of the endogenous component, in order to clarified the difference of the efficacy and effective substances between on T2DM with obesity model to normal groups, and the relevance of active components and microbiota. Furthermore, it will be illuminated that the anti- T2DM mechanism of active compositions of Siraitiae Fructus at three levels: the metabolism of exogenous components, microbiota and the transformation of endogenous components. This study will lay the foundation for the research of pharmacodynamic material, mechanism, and metabolic pathway of active components in vivo, and provide new idea to research and discovery natural products have anti-diabetic activity based on metabolic aspect.