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trimethylamine-N-oxide (TMAO)

Pathology: - atherogenic molecule generated in the liver from absorbed trimethylamine produced by intestinal flora from dietary phosphatidylcholine (meat, eggs) [1,2,3,4,5] - secreted by the liver, it appears in plasma - increased plasma trimethylamine-N-oxide is associated with increased cardiovascular risk - increased mortality in patients with - stable coronary artery disease [3] - peripheral arterial disease [5] - increased mortality in patients with stable CAD - attempts to inhibit formation of trimethylamine-N-oxide from trimethylamine in the liver have resulted in hepatitis [2] - trimethylamine N-oxide is associated with imaging & clinical features of small vessel cerebrovascular disease assessed by white matter hyperintensity volume & lacunar infarcts [6] - increased plasma trimethylamine-N-oxide is associated with increased risk of chronic kidney disease & faster decline in renal function [7] Comparative biology: - 3,3-dimethyl-1-butanol (DMB) inhibits the formation of trimethylamine by intestinal bacteria in mice [2]

General

trimethylamine

Database Correlations

PUBCHEM cid=1145

References

  1. Tang WHW et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013 Apr 25; 368:1575 PMID: 23614584 http://www.nejm.org/doi/full/10.1056/NEJMoa1109400 - Loscalzo J. Gut microbiota, the genome, and diet in atherogenesis. N Engl J Med 2013 Apr 25; 368:1647. PMID: 23614591 http://www.nejm.org/doi/full/10.1056/NEJMe1302154
  2. Wang Z, Roberts AB, Buffa JA et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 2015 Dec 17; 163:1585 PMID: 26687352
  3. Senthong V, Wang Z, Li XS, Fan Y, Wu Y, Tang WH, Hazen SL. Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide and 5-Year Mortality Risk in Stable Coronary Artery Disease: The Contributory Role of Intestinal Microbiota in a COURAGE- Like Patient Cohort. J Am Heart Assoc. 2016 Jun 10;5(6). PMID: 27287696 Free PMC Article
  4. Senthong V, Li XS, Hudec T et al Plasma Trimethylamine N-Oxide, a Gut Microbe-Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden. J Am Coll Cardiol. 2016 Jun 7;67(22):2620-8. PMID: 27256833
  5. Senthong V, Wang Z, Li XS, Fan Y, Wu Y, Tang WH, Hazen SL Trimethylamine N-Oxide and Mortality Risk in Patients With Peripheral Artery Disease. J Am Heart Assoc. 2016; 5: e004237, Online October 19, 2016 PMID: 27287696 Free PMC Article http://jaha.ahajournals.org/content/5/10/e004237.abstract
  6. Kijpaisalratana N, Ament Z, Bevers MB et al Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke. JAMA Netw Open. 2023;6(8):e2330446. PMID: 37610752 PMCID: PMC10448304 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808706
  7. Wang M, Tang WHW, Li X et al The Gut Microbial Metabolite Trimethylamine N-oxide, Incident CKD, and Kidney Function Decline. J Am Soc Nephrol. 2024 Apr 9 PMID: 38593157 https://journals.lww.com/jasn/abstract/9900/the_gut_microbial_metabolite_trimethylamine.282.aspx