基于肠道微生态系统的泽泻提取物改善肥胖小鼠糖脂代谢的体内药效物质及作用机制研究

课题组前期研究表明泽泻提取物(进一步明确为三萜部位)改善高脂诱导肥胖小鼠的糖脂代谢作用显著，并可改善由高脂诱导引起的肥胖小鼠肠道微生物组成，调控肠道菌群功能基因组，为了进一步研究其体内尤其在肠道菌群调控下的调节糖脂代谢药效物质及其作用机制，本研究拟从肠道微生态入手，采用高通量测序技术，通过宏基因组测序-生物信息学探究泽泻对肠道菌群结构组和功能基因组的调控作用；其次，采用肠道代谢结合体内代谢组学-系统生物学分析肠道菌群功能基因组调控后引起的代谢网络的微生态作用，分析泽泻干预后的肠道菌群如何发挥改善糖脂代谢的作用机制，同时也分析泽泻在肠道微生态作用下的内在“显效”形式；第三，拟采用无菌小鼠-泽泻干预后粪便移植法研究泽泻“显效”物质调控的肠道菌群调节肥胖小鼠糖脂作用的菌群代谢物质组及其机制。综合肠道菌群结构组-功能基因组-代谢组-系统生物学阐明泽泻调控肥胖小鼠糖脂代谢的药效物质与分子作用机制。

The preliminary study showed that the effect of the Alismatis Rhizoma (AR) extract (further identified as triterpenoids) on the reduce body weight, improve glycolipid metabolism, change the gut microbiota composition and regulate the functional genomes of gut microbiota in obese mice fed a high-fat diet. In order to study its real material foundation and mechanism of AR, we using the intestinal microecology as the entry point, through the metagenomics-bioinformatics to study the regulation of gut microbiota structure and functional gene by AR; Using metabolomics combine with systems biology analysis to explore the role of AR on intestinal microflora and the internal effective material foundation of AR, and analysis the AR how to play the role on obesity mice. Finally, by using of the germ-free mice and fecal transplantation method to further verify the AR regulating gut microbiota can be improved glycolipid metabolism in obesity germ-free mice and explore the effective metabolites. Clarify the intrinsic mechanism of AR regulate gut microbiota composition - functional genomics - metabolomics, which provides the real material foundation and molecular mechanisms of AR regulating glycolipid metabolism in obesity mice.