Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Your doctor should put this post and the previous one on DMB together to create a stroke prevention protocol. You'll have to hope your doctor is the genius one that can do this right the first time.  OR we could ask our fucking failures of stroke associations  to fail once again at translating research into protocols. But since none of them have an entry point for survivors that won't work at all.

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

• 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

• Affiliations
• Contributions
• Corresponding author

Nature

472,

57–63

(07 April 2011)

doi:10.1038/nature09922

Received

29 July 2009

Accepted

09 February 2011

Published online

06 April 2011

Article tools

• Full text

• PDF

• Citation
• Reprints
• Rights & permissions
• Article metrics

Abstract

• Abstract•
• References•
• Author information•
• Supplementary information

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.