4.3 Review

Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis

Journal

CURRENT OPINION IN LIPIDOLOGY
Volume 27, Issue 2, Pages 148-154

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOL.0000000000000274

Keywords

flavin monooxygenase 3; bile acid; farnesoid X receptor; atherosclerosis; trimethylamine-N-oxide

Funding

  1. Schulich School of Medicine & Dentistry at Western
  2. Canadian Institutes of Health Research/Crohn's Colitis Canada/Canadian Association of Gastroenterology Joint Research Fellowship [201411IBD]
  3. Janssen Incorporated
  4. Wolfe Medical Research Chair in Pharmacogenomics
  5. Canadian Institutes of Health Research [MOP-89753]
  6. Drug Safety and Effectiveness Network (DSEN-PREVENT) [FRN-117588]
  7. Academic Medical Organization of Southwestern Ontario Alternate Funding Plan Innovation Fund
  8. Cancer Care Ontario (CCO) Research Chair Award (Tier-1) in Experimental Therapeutics
  9. Ontario Institute for Cancer Research (OICR) Translational Research Team grant
  10. Canadian Institutes of Health Research

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Purpose of review This article evaluates the link between trimethylamine-N-oxide (TMAO) and bile acids and the consequent impact on the development of atherosclerosis. Recent findings Elevation in plasma TMAO concentrations is associated with an increased risk of cardiovascular disease in many different patient cohorts. In addition to the recently identified direct effects of TMAO on the development of atherosclerosis, other components involved in TMAO metabolism may also have an impact. Furthermore, the relationship between TMAO and bile acid regulation is emerging as a possible mediator of atherosclerosis. Studies that are emerging highlight the mechanistic relationship of TMAO to the development atherosclerosis in addition to its role as disease biomarker. The interplay between TMAO and bile acid metabolism mediated through multiple factors, such as the gut microbiome, farnesoid X receptor signaling, and flavin monooxygenase 3 activity may help identify another pathway by which atherosclerosis occurs. In this review, we discuss the most recent data regarding atherosclerosis, TMAO, and bile acid metabolism.

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