Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure

Journal of Internal Medicine

Volumn 277, Issue 6, 2015, Pages 717-726

  Troseid M ^a,b,c,d   Ueland, T ^b,c,d   Hov, J R ^b,c,d,e,f   Svardal, A ^g   Gregersen, I ^b,d   Dahl, C P ^b,e   Aakhus, S ^b   Gude, E ^b   Bjorndal B ^h   Halvorsen, B ^b,c,d   Karlsen, T H ^b,c,d,e,f,g   Aukrust, P ^b,c,d   Gullestad, L ^d,e,g,h   Berge, R K ^g,h   Yndestad, A ^b,c,d,e  

^a ULLEVÅL UNIVERSITY HOSPITAL   (Norway)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c KG Jebsen Centre for Inflammation Research   (Norway)

^d UNIVERSITY OF OSLO   (Norway)

^e OSLO UNIVERSITY HOSPITAL   (Norway)

^f Clinic for Specialized Medicine and Surgery   (Norway)

^g UNIVERSITY OF BERGEN   (Norway)

^h HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

Gut microbiota; Heart failure; Nutrition; Survival; Trimethylamine N oxide

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; BETAINE; CHOLINE; TRIMETHYLAMINE OXIDE; BIOLOGICAL MARKER; LIPOTROPIC AGENT; METHYLAMINE; OXIDIZING AGENT; TRIMETHYLOXAMINE;

ADULT; ADVERSE OUTCOME; ARTICLE; BODY MASS; CARDIOVASCULAR MORTALITY; COMPARATIVE STUDY; CONGESTIVE CARDIOMYOPATHY; CONTROLLED STUDY; CORONARY ARTERY DISEASE; DISEASE SEVERITY; ESTIMATED GLOMERULAR FILTRATION RATE; FEMALE; GLOMERULUS FILTRATION RATE; HEART CATHETERIZATION; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HEART LEFT VENTRICLE ENDSYSTOLIC VOLUME; HEART OUTPUT; HEART RIGHT ATRIUM PRESSURE; HUMAN; INTESTINE FLORA; LUNG ARTERY PRESSURE; MAJOR CLINICAL STUDY; MALE; OBSERVATIONAL STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; PULMONARY ARTERY OCCLUSION PRESSURE; RIGHT SIDED HEART CATHETERIZATION; SWAN GANZ CATHETER; ULTRASOUND SCANNER; AGED; BLOOD; CHRONIC DISEASE; INTESTINE; METABOLISM; MICROBIOLOGY; MICROFLORA; MIDDLE AGED; MORTALITY; PREDICTIVE VALUE; PROGNOSIS; RISK ASSESSMENT; RISK FACTOR; SENSITIVITY AND SPECIFICITY; SEVERITY OF ILLNESS INDEX; SURVIVAL;

AGED; BETAINE; BIOLOGICAL MARKERS; CHOLINE; CHRONIC DISEASE; FEMALE; HEART FAILURE; HUMANS; INTESTINES; LIPOTROPIC AGENTS; MALE; METHYLAMINES; MICROBIOTA; MIDDLE AGED; OXIDANTS; PREDICTIVE VALUE OF TESTS; PROGNOSIS; PROSPECTIVE STUDIES; RISK ASSESSMENT; RISK FACTORS; SENSITIVITY AND SPECIFICITY; SEVERITY OF ILLNESS INDEX; SURVIVAL ANALYSIS;

EID: 84929655318     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/joim.12328     Document Type: Article

References (26)

1. Aukrust P, Yndestad A, Ueland T, Damas JK, Gullestad L. Anti-inflammatory trials in chronic heart failure. Heart Fail Monit 2006; 5: 2-9.
2. Burcelin R, Serino M, Chabo C, Blasco-Baque V, Amar J. Gut microbiota and diabetes: from pathogenesis to therapeutic perspective. Acta Diabetol 2011; 48: 257-73.
3. Sandek A, Bauditz J, Swidsinski A et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol 2007; 50: 1561-9.
4. Sandek A, Anker SD, von HS. The gut and intestinal bacteria in chronic heart failure. Curr Drug Metab 2009; 10: 22-8.
5. Charalambous BM, Stephens RC, Feavers IM, Montgomery HE. Role of bacterial endotoxin in chronic heart failure: the gut of the matter. Shock 2007; 28: 15-23.
6. Tang WH, Wang Z, Levison BS et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368: 1575-84.
7. Backhed F. Meat-metabolizing bacteria in atherosclerosis. Nat Med 2013; 19: 533-4.
8. Koeth RA, Wang Z, Levison BS et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19: 576-85.
9. Wang Z, Tang WH, Buffa JA et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J 2014; 35: 904-10.
10. Ueland T, Dahl CP, Gullestad L et al. Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin Sci (Lond) 2011; 121: 119-27.
11. Yndestad A, Finsen AV, Ueland T et al. The homeostatic chemokine CCL21 predicts mortality and may play a pathogenic role in heart failure. PLoS ONE 2012; 7: e33038.
12. Ueland T, Svardal A, Oie E et al. Disturbed carnitine regulation in chronic heart failure-increased plasma levels of palmitoyl-carnitine are associated with poor prognosis. Int J Cardiol 2013; 167: 1892-9.
13. Bjorndal B, Burri L, Wergedahl H, Svardal A, Bohov P, Berge RK. Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFalpha. Eur J Nutr 2012; 51: 741-53.
14. Troseid M, Nestvold TK, Rudi K, Thoresen H, Nielsen EW, Lappegard KT. Plasma lipopolysaccharide is closely associated with glycemic control and abdominal obesity: evidence from bariatric surgery. Diabetes Care 2013; 35: 3627-32.
15. Hartiala J, Bennett BJ, Tang WH et al. Comparative genome-wide association studies in mice and humans for trimethylamine N-oxide, a proatherogenic metabolite of choline and L-carnitine. Arterioscler Thromb Vasc Biol 2014; 34: 1307-13.
16. Wang Z, Klipfell E, Bennett BJ et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472: 57-63.
17. Bennett BJ, de Aguiar Vallim TQ, Wang Z et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab 2013; 17: 49-60.
18. Konstantinova SV, Tell GS, Vollset SE, Nygard O, Bleie O, Ueland PM. Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 2008; 138: 914-20.
19. Letoffe S, Audrain B, Bernier SP, Delepierre M, Ghigo JM. Aerial exposure to the bacterial volatile compound trimethylamine modifies antibiotic resistance of physically separated bacteria by raising culture medium pH. MBio 2014; 5: e00944-13.
20. Craciun S, Balskus EP. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci U S A 2012; 109: 21307-12.
21. Zhu Y, Jameson E, Crosatti M et al. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc Natl Acad Sci U S A 2014; 111: 4268-73.
22. Verbrugge FH, Dupont M, Steels P et al. Abdominal contributions to cardiorenal dysfunction in congestive heart failure. J Am Coll Cardiol 2013; 62: 485-95.
23. Bain MA, Faull R, Fornasini G, Milne RW, Evans AM. Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol Dial Transplant 2006; 21: 1300-4.
24. Vinje S, Stroes E, Nieuwdorp M, Hazen SL. The gut microbiome as novel cardio-metabolic target: the time has come!. Eur Heart J 2014; 25: 883-7.
25. Kumemoto R, Yusa K, Shibayama T, Hatori K. Trimethylamine N-oxide suppresses the activity of the actomyosin motor. Biochim Biophys Acta 2012; 1820: 1597-604.
26. Ashaye A, Gaziano J, Djousse L. Red meat consumption and risk of heart failure in male physicians. Nutr Metab Cardiovasc Dis 2011; 21: 941-6.