Intestinal Flora Derived Metabolites Affect the Occurrence and Development of Cardiovascular Disease

Yinuo Wen,1,2,* Zefan Sun,1,* Shuoyin Xie,1,2 Zixuan Hu,1,2 Qicheng Lan,1,2 Yupeng Sun,1,2 Linbo Yuan,3 Changlin Zhai1,2 1The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China; 2The First Clinical College, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changlin Zhai, The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China, Email yesterdaygun@126.com Linbo Yuan, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email ylb@wmu.edu.cnAbstract: In recent years, increasing evidence has shown that the gut microbiota and their metabolites play a pivotal role in human health and diseases, especially the cardiovascular diseases (CVDs). Intestinal flora imbalance (changes in the composition and function of intestinal flora) accelerates the progression of CVDs. The intestinal flora breaks down the food ingested by the host into a series of metabolically active products, including trimethylamine N-Oxide (TMAO), short-chain fatty acids (SCFAs), primary and secondary bile acids, tryptophan and indole derivatives, phenylacetylglutamine (PAGln) and branched chain amino acids (BCAA). These metabolites participate in the occurrence and development of CVDs via abnormally activating these signaling pathways more swiftly when the gut barrier integrity is broken down. This review focuses on the production and metabolism of TMAO and SCFAs. At the same time, we summarize the roles of intestinal flora metabolites in the occurrence and development of coronary heart disease and hypertension, pulmonary hypertension and other CVDs. The theories of “gut-lung axis” and “gut-heart axis” are provided, aiming to explore the potential targets for the treatment of CVDs based on the roles of the intestinal flora in the CVDs.Keywords: cardiovascular diseases, intestinal microecology, trimethylamine oxide, short-chain fatty acids, gut-heart axis