PMID- 25382824
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20220408
IS  - 1365-2796 (Electronic)
IS  - 0954-6820 (Linking)
VI  - 277
IP  - 6
DP  - 2015 Jun
TI  - Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease 
      severity and survival of patients with chronic heart failure.
PG  - 717-26
LID - 10.1111/joim.12328 [doi]
AB  - OBJECTIVES: Recent metabolomic, experimental and clinical studies have 
      demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent 
      metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor 
      of coronary artery disease (CAD). This finding suggests a link between the gut 
      microbiota and atherosclerosis. The potential impact of TMAO in chronic heart 
      failure (HF) is unknown. We hypothesized that TMAO levels would provide 
      prognostic information about adverse outcomes in chronic HF. DESIGN: Prospective, 
      observational study including 155 consecutive patients with chronic HF. In 
      addition, 100 patients with stable CAD without HF and 33 matched healthy 
      individuals were included as controls. Plasma levels of TMAO and its precursors 
      choline and betaine were measured, and associations with symptoms, aetiology and 
      transplant-free survival in the patients with HF were explored. RESULTS: Plasma 
      levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were 
      elevated in patients with chronic HF compared to control subjects, with the 
      highest levels in patients with New York Heart Association (NYHA) classes III and 
      IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, 
      followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or 
      betaine, was associated with reduced transplant-free survival: approximately 50% 
      of patients in the upper tertile of TMAO levels died or received a heart 
      transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 
      2.24, 95% confidence interval 1.28-3.92, P = 0.005). CONCLUSIONS: TMAO levels 
      were elevated in patients with HF and associated with NYHA class, ischaemic 
      aetiology and adverse outcomes. Future studies should focus on gut microbiota, 
      dietary composition and intestinal dysfunction in relation to TMAO levels and 
      clinical outcome in HF.
CI  - (c) 2014 The Association for the Publication of the Journal of Internal Medicine.
FAU - Troseid, M
AU  - Troseid M
AD  - Department of Infectious Diseases, Oslo University Hospital, Ulleval, Norway.
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
AD  - Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital 
      Rikshospitalet, Norway.
FAU - Ueland, T
AU  - Ueland T
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
FAU - Hov, J R
AU  - Hov JR
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
AD  - Department of Transplantation Medicine, Section of Gastroenterology, Oslo 
      University Hospital, Norway.
AD  - Norwegian PSC Research Center, Norway.
FAU - Svardal, A
AU  - Svardal A
AD  - Department of Clinical Science, University of Bergen, Norway.
FAU - Gregersen, I
AU  - Gregersen I
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
FAU - Dahl, C P
AU  - Dahl CP
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - Department of Cardiology, Oslo University Hospital, Rikshospitalet, Norway.
AD  - Centre for Heart Failure Research, Oslo University Hospital, Norway.
FAU - Aakhus, S
AU  - Aakhus S
AD  - Department of Cardiology, Oslo University Hospital, Rikshospitalet, Norway.
FAU - Gude, E
AU  - Gude E
AD  - Department of Cardiology, Oslo University Hospital, Rikshospitalet, Norway.
FAU - Bjorndal, B
AU  - Bjorndal B
AD  - Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
FAU - Halvorsen, B
AU  - Halvorsen B
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
FAU - Karlsen, T H
AU  - Karlsen TH
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
AD  - Department of Transplantation Medicine, Section of Gastroenterology, Oslo 
      University Hospital, Norway.
AD  - Norwegian PSC Research Center, Norway.
AD  - Division of Gastroenterology, Institute of Medicine, University of Bergen, 
      Bergen, Norway.
FAU - Aukrust, P
AU  - Aukrust P
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
AD  - Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital 
      Rikshospitalet, Norway.
FAU - Gullestad, L
AU  - Gullestad L
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
AD  - Department of Clinical Science, University of Bergen, Norway.
AD  - Centre for Heart Failure Research, Oslo University Hospital, Norway.
AD  - Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
AD  - K.G. Jebsen Cardiac Research Center, University of Oslo, Oslo, Norway.
FAU - Berge, R K
AU  - Berge RK
AD  - Department of Clinical Science, University of Bergen, Norway.
AD  - Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
FAU - Yndestad, A
AU  - Yndestad A
AD  - Research Institute of Internal Medicine, Oslo University Hospital, 
      Rikshospitalet, Norway.
AD  - K.G. Jebsen Centre for Inflammation Research, Norway.
AD  - Institute of Clinical Medicine, University of Oslo, Norway.
AD  - Centre for Heart Failure Research, Oslo University Hospital, Norway.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141201
PL  - England
TA  - J Intern Med
JT  - Journal of internal medicine
JID - 8904841
RN  - 0 (Biomarkers)
RN  - 0 (Lipotropic Agents)
RN  - 0 (Methylamines)
RN  - 0 (Oxidants)
RN  - 3SCV180C9W (Betaine)
RN  - FLD0K1SJ1A (trimethyloxamine)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Aged
MH  - Betaine/*blood
MH  - Biomarkers/blood
MH  - Choline/*blood
MH  - Chronic Disease
MH  - Female
MH  - Heart Failure/blood/*diagnosis/metabolism/mortality
MH  - Humans
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/*microbiology
MH  - Lipotropic Agents/*blood
MH  - Male
MH  - Methylamines/*blood
MH  - *Microbiota
MH  - Middle Aged
MH  - Oxidants/*blood
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Prospective Studies
MH  - Risk Assessment
MH  - Risk Factors
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Survival Analysis
OTO - NOTNLM
OT  - gut microbiota
OT  - heart failure
OT  - nutrition
OT  - survival
OT  - trimethylamine-N-oxide
EDAT- 2014/11/11 06:00
MHDA- 2015/09/22 06:00
CRDT- 2014/11/11 06:00
PHST- 2014/11/11 06:00 [entrez]
PHST- 2014/11/11 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
AID - 10.1111/joim.12328 [doi]
PST - ppublish
SO  - J Intern Med. 2015 Jun;277(6):717-26. doi: 10.1111/joim.12328. Epub 2014 Dec 1.