Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide.

Aims: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients.

Methods And Results: We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography.

Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk.

Background: Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans.

Methods: We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics.

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism.

Detectable subclinical myocardial necrosis is associated with cardiovascular risk in stable patients with diabetes.

Objective: To investigate the relationship between different degrees of subclinical myocardial necrosis, glycemic control, and long-term adverse clinical outcomes within a stable patient population with diabetes mellitus.

Research Design And Methods: We examined 1,275 stable patients with diabetes mellitus undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (MI) (<0.03 ng/mL).

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD.