Gut microbiome and metabolites, the future direction of diagnosis and treatment of atherosclerosis?

Abstract

Over the past few decades, the treatment of atherosclerotic cardiovascular disease has mainly been through an LDL lowering strategy and treatments targeting other traditional risk factors for atherosclerosis, which has significantly reduced cardiovascular mortality. However, the overall benefit of targeting these risk factors has stagnated, and the discovery of new therapeutic targets for atherosclerosis remains a challenge. Accumulating evidence from clinical and animal experiments has revealed that the gut microbiome play a significant role in human health and disease, including cardiovascular diseases. The gut microbiome contribute to host health and disease through microbial composition and function. The gut microbiome function like an endocrine organ by generating bioactive metabolites that can impact atherosclerosis. In this review, we describe two gut microbial metabolites/pathways by which the gut affects atherosclerotic cardiovascular disease. On the one hand, we discuss the effects of trimethylamine oxide (TMAO), bile acids and aromatic amino acid metabolites on the development of atherosclerosis, and the protective effects of beneficial metabolites short chain amino acids and polyamines on atherosclerosis. On the other hand, we discuss novel therapeutic strategies for directly targeting gut microbial metabolites to improve cardiovascular outcomes. Reducing gut-derived TMAO levels and interfering with the bile acid receptor farnesoid X receptor (FXR) are new therapeutic strategies for atherosclerotic disease. Enzymes and receptors in gut microbiota metabolic pathways are potential new drug targets. We need solid insight into these underlying mechanisms to pave the way for therapeutic strategies targeting gut microbial metabolites/pathways for atherosclerotic cardiovascular disease.

Keywords: Atherosclerosis; Bile acids; Gut microbiome; Metabolites; TMAO.