Metaorganismal nutrient metabolism as a basis of... : Current Opinion in Lipidology (original) (raw)

NUTRITION AND METABOLISM: Edited by Frank M. Sacks and Lawrence J. Appel

Metaorganismal nutrient metabolism as a basis of cardiovascular disease

Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA

Correspondence to Stanley L. Hazen, MD, PhD, 9500 Euclid Avenue, NC-10, Cleveland Clinic, Cleveland, OH 44195, USA. Tel: +1 216 445 9763; fax: +1 216 444 9404; e-mail: [email protected]

Abstract

Purpose of review

Atherosclerosis and associated cardiovascular disease (CVD) remains the leading cause of mortality in Western societies. It is well accepted that the consumption of foods abundant in saturated fats and cholesterol, like meats, egg yolk and high-fat dairy products, are associated with increased CVD risk. New evidence suggests that trimethylamine (TMA)-containing nutrients within these foods, including phosphatidylcholine, choline, and L-carnitine, can enter into a microbial metabolic pathway that promotes CVD. In this review, we highlight the role of gut microbiota-driven nutrient metabolism as a novel pathway promoting CVD.

Recent findings

Recent studies demonstrate a link between ingestion of dietary phosphatidylcholine, choline, and L-carnitine and CVD risk. At the center of this pathway is gut microbiota-dependent synthesis of a metabolic intermediate called TMA, and subsequent host-driven conversion of TMA to trimethylamine-_N_-oxide (TMAO). Microbiota-dependent generation of TMAO is associated with increased risk of incident major adverse cardiovascular events in humans, and provision of TMAO promotes atherosclerosis in mice.

Summary

Microbial metabolism of TMA containing nutrients can lead to formation of the proatherogenic compound TMAO. Recent insights into this diet–microbe–host interaction provide new clues surrounding the pathogenesis of atherosclerosis, and may serve as a framework for new CVD therapies.