Targeting a Potent New Risk Factor for Atherosclerosis via the Gut Microbiome

In 2013, researchers reported on a potent new risk factor for atherosclerosis, trimethylamine-N-oxide (TMAO; NEJM JW Gen Med Ju1 1 2013 and Nat Med 2013; 19:576). Gut microbes metabolize nutrients in food, particularly choline and L-carnitine, and produce trimethylamine (TMA), which is transformed by a liver enzyme into TMAO. Circulating TMAO levels in humans correlate with atherosclerosis burden.

TMAO production can be reduced by inhibiting the liver enzyme that produces it, but this causes adverse effects — particularly hepatic inflammation. To avoid this adverse effect, a team from Cleveland Clinic sought to lower TMAO levels by inhibiting bacterial production of TMA. They identified a small molecule, 3,3-dimethyl-1-butanol (DMB), that in…