The Role of Gut-Microbiota in Atherosclerosis and Cardiovascular Disease

A variety of microorganisms colonize the human body and are important for human health. They play a role in the digestion and absorption of key nutrients from the diet, but have also been implicated in disease. Gut-microbiota can metabolize various quaternary amines, such as phosphatidylcholine, choline, and L-carnitine to trimethylamine (TMA). TMA is then hepatically oxidized to trimethylamine-N-oxide (TMAO). TMAO is known to promote atherosclerosis by reducing reverse cholesterol transport via proposed mechanisms including the up-regulation of macrophage scavenger receptors and/or the bile acid synthetic pathway. Additionally, elevated levels of this metabolite have been linked to an increased risk for cardiovascular disease. Removal of choline, carnitine, and other TMAO precursors from the diet is not recommended since these essential nutrients are required for physiological processes. Instead, treatment should be targeted at reducing the conversion of precursors to TMA or TMAO. A promising therapeutic approach includes the use of meldonium to inhibit the carnitine biosynthetic pathway and reduce levels of TMA/TMAO. Further investigations into the biochemical mechanisms involved in trimethylamine formation can accelerate the development of more feasible treatment strategies.