IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v472y2011i7341d10.1038_nature09922.html
   My bibliography  Save this article

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Author

Listed:
  • Zeneng Wang

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Elizabeth Klipfell

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Brian J. Bennett

    (BH-307 Center for the Health Sciences, University of California, Los Angeles, California 90095, USA)

  • Robert Koeth

    (Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Bruce S. Levison

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Brandon DuGar

    (Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Ariel E. Feldstein

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Earl B. Britt

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Xiaoming Fu

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Yoon-Mi Chung

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Yuping Wu

    (Cleveland State University, Cleveland, Ohio 44115, USA)

  • Phil Schauer

    (Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Jonathan D. Smith

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Hooman Allayee

    (Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA)

  • W. H. Wilson Tang

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Joseph A. DiDonato

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA)

  • Aldons J. Lusis

    (BH-307 Center for the Health Sciences, University of California, Los Angeles, California 90095, USA)

  • Stanley L. Hazen

    (Cleveland Clinic, Cleveland, Ohio 44195, USA
    Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Cleveland Clinic, Cleveland, Ohio 44195, USA)

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.

Suggested Citation

  • 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 & Jo, 2011. "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease," Nature, Nature, vol. 472(7341), pages 57-63, April.
    • Handle: RePEc:nat:nature:v:472:y:2011:i:7341:d:10.1038_nature09922
    DOI: 10.1038/nature09922
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature09922
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature09922?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Zahraa Al Bander & Marloes Dekker Nitert & Aya Mousa & Negar Naderpoor, 2020. "The Gut Microbiota and Inflammation: An Overview," IJERPH, MDPI, vol. 17(20), pages 1-21, October.
    2. Chiu-Huang Kuo & Chin-Hung Liu & Ji-Hung Wang & Bang-Gee Hsu, 2022. "Serum Trimethylamine N-Oxide Levels Correlate with Metabolic Syndrome in Coronary Artery Disease Patients," IJERPH, MDPI, vol. 19(14), pages 1-9, July.
    3. Nicole Farmer & Cristhian A. Gutierrez-Huerta & Briana S. Turner & Valerie M. Mitchell & Billy S. Collins & Yvonne Baumer & Gwenyth R. Wallen & Tiffany M. Powell-Wiley, 2021. "Neighborhood Environment Associates with Trimethylamine-N-Oxide (TMAO) as a Cardiovascular Risk Marker," IJERPH, MDPI, vol. 18(8), pages 1-15, April.
    4. Ruth Nussinov & Jason A Papin, 2017. "How can computation advance microbiome research?," PLOS Computational Biology, Public Library of Science, vol. 13(9), pages 1-3, September.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:472:y:2011:i:7341:d:10.1038_nature09922. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.