Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
- PMID: 21475195
- PMCID: PMC3086762
- DOI: 10.1038/nature09922
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Abstract
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.
©2011 Macmillan Publishers Limited. All rights reserved
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Comment in
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Cardiovascular disease: the diet-microbe morbid union.Nature. 2011 Apr 7;472(7341):40-1. doi: 10.1038/472040a. Nature. 2011. PMID: 21475185 No abstract available.
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Recent highlights of metabolomics in cardiovascular research.Circ Cardiovasc Genet. 2011 Aug 1;4(4):463-4. doi: 10.1161/CIRCGENETICS.111.961003. Circ Cardiovasc Genet. 2011. PMID: 21846870 No abstract available.
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Flagging flora: heart disease link.Nature. 2011 Sep 7;477(7363):162. doi: 10.1038/477162d. Nature. 2011. PMID: 21900997 No abstract available.
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References
-
- Epstein SE, et al. The role of infection in restenosis and atherosclerosis: focus on cytomegalovirus. Lancet. 1996;348(Suppl 1):s13–17. - PubMed
-
- Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? The Lancet. 1997;350:430–436. - PubMed
-
- Saikku P, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. The Lancet. 1988;332:983–986. - PubMed
-
- O'Connor CM, et al. Azithromycin for the Secondary Prevention of Coronary Heart Disease Events: The WIZARD Study: A Randomized Controlled Trial. JAMA. 2003;290:1459–1466. - PubMed
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