结肠菌群介导大豆异黄酮生物转化S-雌马酚的作用机理研究

S-雌马酚（Eq）是大豆异黄酮（SI）经结肠菌群代谢产生的微生物转化物，其类雌激素活性及抗氧化作用介导了广泛的健康生物学效应，但40-70%人群不能将SI有效生物转化为Eq。 由于肠道菌群的多样性和复杂性，导致我们对SI在结肠与菌群互作代谢机制知之甚少。本课题拟采用Eq产生者粪便构建C57BL/6J HFA模型小鼠，用SI对模型小鼠结肠菌群进行干涉，利用宏基因组高通量测序技术对结肠菌群结构变化规律进行分析，筛选获得上调的优势菌群种类；利用宏转录组RNA-Seq技术获得差异表达基因，通过功能注释筛选SI代谢过程中的关键功能基因；结合代谢物组关联分析推定SI在小鼠结肠代谢Eq的通路；在此基础，通过体外富集和纯培养技术分离相关菌群进行逐步验证，阐明SI代谢过程中结肠菌群-关键基因-代谢产物间的相互关系，揭示结肠菌群调控SI生物转化Eq的作用机理，为膳食与肠道菌群互作影响健康作用机制研究奠定基础。

The soy isoflavone is activated to S-equol exclusively by colonic flora. S-equol shows a wide range of potential health benefits by possessing estrogenic activities and anti-oxidant properties. However, 40-70% of healthy adult persons aren’t able to produce S-equol following ingestion of soy isoflavone. The metabolism mechanism between soy isoflavone and colonic flora is poorly understood because of the diversity and complexity of intestinal flora. In this study, C57BL/6J HFA mice model will be constructed by planting equol producer stool suspension and then soy isoflavone will be used to interfere with the colonic flora of model mice. The up-regulated dominant bacteria are supposed to be screened out by analyzing change rules of colonic flora structure using metagenome high-throughput sequencing technique. The key functional genes modulated in the process of soy isoflavone metabolism are planned to be screened out by functional annotation of differentially expressed genes by using macro transcriptome RNA-Seq technology. The pathway of biotransformation from soy isoflavone to S-equol will be confirmed based on associated analysis of metabolites group and functional genes. On this basis, the related bacteria will be isolated for confirmation through vitro enrichment and pure culture step by step. The interference relations among colonic flora, key functional genes and metabolism products will be clarified and the mechanism of biotransformation of soy isoflavone to S-equol will be revealed. This project will provide a theoretical basis for supporting human health by studying the interaction mechanism between dietary composition and colonic flora.