Potential effects of natural dietary compounds on trimethylamine Noxide (TMAO) formation and TMAO-induced atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death worldwide. Recently, trimethylamine N-oxide (TMAO) is identified to be highly associated with CVD development and exacerbates atherosclerosis by several mechanisms. TMAO is a gut microbiota-dependent metabolite formed from dietary quaternary amines, mainly choline and carnitine. These trimethylamine (TMA)-containing compounds are first converted to TMA by enzymes in gut microbiota and subsequently metabolized by the host hepatic enzymes to TMAO. As the microbiome is the source of TMAO, administration of broad spectrum antibiotics shows marked decrease in TMAO levels. However, antibiotics may possess many possible undesirable side effects and chronic treatment consideration effects of antibiotic resistance in bacteria. Thus, studies have focused on the alternative strategies, including use of natural dietary compounds to reduce elevated TMAO levels and prevent atherogenesis. Natural dietary compounds have been studied for their beneficial health effects for decades. Diet and nutritional interventions based on the use of natural bioactive compounds is an effective strategy for remodeling gut microbiota composition and improving human health. This review focuses on the mechanisms by which TMAO promote atherosclerosis, the microbes that contribute to TMA formation, the enzymes involved, and the potential of natural dietary compounds that contribute to TMAO reduction and attenuate TMAO-induced atherosclerosis.