Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-04-06

AUTHORS

Zeneng Wang, Elizabeth Klipfell, Brian J. Bennett, Robert Koeth, Bruce S. Levison, Brandon DuGar, Ariel E. Feldstein, Earl B. Britt, Xiaoming Fu, Yoon-Mi Chung, Yuping Wu, Phil Schauer, Jonathan D. Smith, Hooman Allayee, W. H. Wilson Tang, Joseph A. DiDonato, Aldons J. Lusis, Stanley L. Hazen

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. More... »

PAGES

57-63

Journal

TITLE

Nature

ISSUE

7341

VOLUME

472

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09922

    DOI

    http://dx.doi.org/10.1038/nature09922

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043309820

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21475195


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