基于高尿酸血症与肠道菌群及其代谢产物相关性的穿山龙总皂苷干预作用研究

Hyperuricemia (HUA) is a public health problem that needs to be solved urgently, and its incidence increases year by year. The correlation between HUA with gut microbiota and its metabolites SCFAs has been confirmed by research, revealed that the relative abundances of the nucleotide metabolism and metabolic diseases were increased in the hyperuricemia model. There were uric acid reducing effect of total saponins from Rhizoma Dioscoreae Nipponicae that are mostly metabolized in the intestine. It is concluded that the dynamic changes in the gut microbiota directly affect the metabolism of HUA in vivo. This project intends to study the relationship between gut microbiota and its metabolites with HUA based the intervention of total saponins from Rhizoma Dioscoreae Nipponicae. Metabolomics and metagenomics methods will be used to found the relationship between microbial population changes and metabolites changes through the bioinformatics related the changes in small molecule differential metabolites, metabolic pathways, the functions and metabolites of gut microbiota species. Finally, it was clarified that the total saponins from Rhizoma Dioscorea nipponica achieved the effect of lowering blood uric acid by regulating the dynamic balance of gut microbiota that inhibits uric acid production and promotes the excretion of uric acid, providing a theoretical basis for the development of personalized Chinese medicine preparation targeting the gut microbiota.

高尿酸血症（HUA）发病率逐年升高，是亟待解决的公共健康问题。研究证实HUA与肠道菌群及其代谢产物SCFAs存在相关性，高尿酸血症模型中肠道菌群Nuleotide Metabolism（核苷酸代谢）和Metabolic Diseases（代谢性疾病）相对丰度表达均上调；穿山龙总皂苷的皂苷类成分大多在肠道中被代谢，且有较好降尿酸作用。由此推断，肠道微生态动态变化直接影响HUA体内代谢。本课题拟研究肠道菌群及其代谢产物和HUA相关性，以穿山龙总皂苷干预为切入点，运用代谢组学、宏基因组学方法将分析得到的与高尿酸血症相关的小分子差异代谢物、代谢通路、肠道菌群物种、功能及代谢物含量变化进行生物信息学关联，找到菌群变化与代谢物变化之间的关系，最终阐明穿山龙总皂苷通过调控肠道菌群动态平衡及其代谢产物合成，抑制尿酸生成促进尿酸排泄来实现降低血尿酸的作用，为开发以肠道菌群为靶点的个性化中药制剂提供理论依据。

高尿酸血症（HUA）发病率逐年升高，是亟待解决的公共健康问题。本课题以穿山龙总皂苷干预为切入点，运用代谢组学、宏基因组学技术探讨肠道菌群及其代谢产物与HUA的关系。发现穿山龙总皂苷具有明显的降尿酸作用，其中以高剂量给药组效果最好；从尿液、血清及粪便代谢组学分别发现55种、41种及19种差异代谢物，药物干预能回调16种、23种及7种代谢物，主要涉及氨基酸代谢途径和核苷酸代谢途径；通过GS-MS联合检测短链脂肪酸（SCFAs），发现粪便中7种SCFAs能够有效分离，药物干预后，各种SCFAs含量呈不同程度的下降趋势，其中以己酸的含量变化最为显著；16S rRNA测序发现样本组间菌群结构差异明显，找到厚壁菌门、变形杆菌门和拟杆菌门3个差异菌门；乳杆菌属、粪球菌属、示波螺菌属、瘤胃球菌属、异杆菌属5个差异菌属。根据菌群群落结构的变化可预测药物干预前后有6条与尿酸调节相关的功能代谢通路；宏基因组学测序发现穿山龙总皂苷能够特异性的改善高尿酸血症大鼠肠道菌群门、属、种水平差异水平的丰度，差异基因参与了果糖和甘露糖代谢、泛醌和其他萜醌类生物合成等多条代谢通路及代谢过程；通过对差异代谢物和宏基因组学差异基因基于代谢通路的联合分析，结果显示穿山龙总皂苷干预高尿酸血症主要是通过干预大鼠及其肠道菌群的ABC转运体通路、组氨酸代谢通路、酪氨酸代谢通路等生物学途径发挥作用。最终阐明穿山龙总皂苷通过调控肠道菌群动态平衡及其代谢产物合成，抑制尿酸生成促进尿酸排泄来实现降低血尿酸的作用，为开发以肠道菌群为靶点的个性化中药制剂提供理论依据。