**Abstract**

Atherosclerosis (AS) is the common pathological underpinning of numerous cardiovascular illnesses (CVDs), and it is the leading cause of death worldwide. In recent years, researchers have begun to recognize the importance of gut microbiota in AS. Gut microbial dysbiosis has been reported to be connected with various CVDs. Moreover, dietary choline, betaine, and L-carnitine produce trimethylamine N-oxide (TMAO), a key gut microbe-dependent metabolite. Multiple studies have found a link between plasma TMAO levels and the likelihood of developing AS. The mechanism underlying this link, however, is still unknown. In this chapter, we discuss the TMAOmediated mechanisms of atherosclerotic CVD from the perspectives of dietary patterns and gut microbial metabolism. Finally, we explain how TMAO has emerged as a novel therapeutic target for CVDs, as well as many treatment options for lowering TMAO levels that are currently being investigated, such as medications, dietary changes, probiotics, and so on.

**Keywords:** cardiovascular disease, gut microbiota, trimethylamine (TMA), trimethylamine-N-oxide (TMAO), diet, metabolism
