Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Apr 9, 2011Nature

Gut bacteria breaking down phosphatidylcholine may increase heart disease risk

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Abstract

Three metabolites of dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO), and betaine—predict risk for cardiovascular disease (CVD).

Metabolomics profiles in plasma can identify small molecules linked to cardiovascular disease risk.
Dietary supplementation with choline or TMAO was associated with increased atherosclerosis in mice.
Germ-free mice studies indicated that gut flora is essential for TMAO production from dietary choline.
Intestinal microflora suppression in atherosclerosis-prone mice reduced dietary choline's impact on atherosclerosis.
Genetic variations affecting flavin monooxygenases correlated with atherosclerosis in hyperlipidaemic mice.

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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. Three metabolites of the dietary lipid phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

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Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

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