The role of gut-microbiota in atherosclerosis and cardiovascular disease

Main Article Content

Whitney Faiella

Keywords

microbiota, intestine, gut, trimethylamines, TMAO, atherosclerosis, cardiovascular disease, choline, phosphatidylcholine, carnitine

Abstract

A variety of microorganisms colonize the intestines 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 the up-regulation of macrophage scavenger receptors and increased foam cell formation. 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. Treatment should rather be targeted at reducing the conversion of precursors to TMA or TMAO. Therapeutic agents have targeted the suppression of intestinal microbiota using antibiotics to prevent the conversion of precursors to TMAO. A more promising 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.