Flavonifractor plautii Protects Against Elevated Arterial Stiffness

作者：Shiyun Luo, Yawen Zhao, Shanshan Zhu, Ludi Liu, Ken Cheng, Bingqi Ye, Yueyuan Han, Jiahua Fan, Min Xia · 发表于：Circulation Research · 年份：2022 · DOI：10.1161/circresaha.122.321975 · 被引用次数：65 · 研究领域：Cardiovascular Health and Disease Prevention、Atherosclerosis and Cardiovascular Diseases、Gut microbiota and health

Background: Dysbiosis of gut microbiota plays a pivotal role in vascular dysfunction and microbial diversity was reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown. Methods: Participants with elevated arterial stiffness and normal controls free of medication were matched for age and sex. The microbial composition and metabolic capacities between the 2 groups were compared with the integration of metagenomics and metabolomics. Subsequently, Ang II (angiotensin II)-induced and humanized mouse model were employed to evaluate the protective effect of Flavonifractor plautii ( F plautii ) and its main effector cis-aconitic acid. Results: Human fecal metagenomic sequencing revealed a significantly high abundance and centrality of F plautii in normal controls, which was absent in the microbial community of subjects with elevated arterial stiffness. Moreover, blood pressure only mediated part of the effect of F plautii on lower arterial stiffness. The microbiome of normal controls exhibited an enhanced capacity for glycolysis and polysaccharide degradation, whereas, those of subjects with increased arterial stiffness were characterized by increased biosynthesis of fatty acids and aromatic amino acids. Integrative analysis with metabolomics profiling further suggested that increased cis-a...