单形拟杆菌通过代谢产物甘油二酯和叶酸调控动脉粥样硬化的作用及机制研究

动脉粥样硬化(AS)是全球范围人类死亡的主要原因之一。肠道菌群的代谢衍生物短链脂肪酸(SCFA)抑制AS的发生，而氧化三甲胺(TMAO)促进AS的发生，但是更多作用机制还不清晰。前期工作中，通过瑞典和中国的AS队列的肠道宏基因组数据挖掘，发现病人的菌群显著缺乏甘油二酯生物合成、叶酸转化、四氢叶酸生物合成等功能通路；Faecalibacterium prausnitzii对甘油二酯生物合成起最主要贡献，而Bacteroides uniformis对这三个通路均起主要贡献。于是猜想B. uniformis可能通过代谢产物甘油二酯和叶酸调控AS。本申请利用ApoE−/−的小鼠构建AS动物模型，分别补充B. uniformis和F. prausnitzii，探究其对小鼠肠道菌群、血清代谢组和病理的影响。该项目将为AS发病机制的研究、新型益生菌的研发以及治疗药物的筛选带来巨大的科学和应用价值。

Atherosclerosis (AS) is one of the leading causes of death in humans worldwide. Gut microbiota derived metabolites short-chain fatty acids (SCFA) and trimethylamine oxide (TMAO) suppress or promote the development of AS, respectively; however, more mechanisms remain unclear. In the previous work, we analyzed the gut metagenome of the AS cohorts from Sweden and China, and results showed the microbiota of the patients were relatively depleted in functional pathways including diacylglycerol biosynthesis, folate transformations and N10-formyl-tetrahydrofolate biosynthesis. Faecalibacterium prausnitzii makes the most contribution to diacylglycerol biosynthesis, while Bacteroides uniformis greatly contributes to these pathways. Therefore, we hypothesize that B. uniformis may regulate AS through the metabolites diacylglycerol and folate. The application aims to construct an AS animal model using ApoE-/- mice, then supplement B. uniformis and F. prausnitzii to explore their effects on the gut microbiome, serum metabolome, and pathology. It is of great importance in scientific and practical applications to study the pathogenesis of AS, research and development of new probiotics, and screening of therapeutic drugs.