The Intricate Gut-Heart Connection; Role of Gut Microbiota in the Pathogenesis of Cardiovascular Disease

Author(s): Amelia Freeman, Govindi Harricharran, Maxim Crasta

The human intestines are home to a complex community of bacterial organisms known as the gut microbiome. The composition of the microbiome is susceptible to modifications triggered by environmental factors and lifestyle choices made by the host. The interactions between the gut microbiome and the host have a crucial role in regulating human health and can influence various metabolic pathways, leading to potential health consequences. One such consequence is cardiovascular disease (CVD), which is the leading cause of death worldwide. CVD encompasses any disease process affecting the heart or blood vessels and has been shown to be affected by microbial imbalances in the gut. Specifically, conditions such as atherosclerosis, hypertension, and heart failure have been linked to dysbiosis within the gut microbiome. Specific by-products of microbial metabolism, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids (BAs), are contributors to this imbalance. TMAO is a proatherogenic metabolite that is derived from the breakdown of dietary choline and L-carnitine and has been found to cause abnormalities in platelet function and lipid levels, as well as increases in oxidative stress. SCFAs are produced when the gut microbiome ferments carbohydrates. This article will focus on three specific SCFAs: butyrate, acetate, and propionate. Butyrate has anti-inflammatory properties in the body, while acetate and propionate play roles in cholesterol production. Additionally, propionate may also contribute to vascular dysfunction, hypertension, and hypertrophy. The gut microbiome can convert primary bile into secondary BAs. These secondary BAs have been linked to higher levels of cholesterol and the development of CVD. By understanding the connection between CVD and the gut microbiome, we can decipher the mechanisms that contribute to heart disease. In this article, we will examine how these microbial-synthesized metabolites impact CVD and explore potential treatments for gut dysbiosis such as microbial transplants and probiotics.