Circulating trimethylamine-N-oxide is associated with all-cause mortality in subjects with nonalcoholic fatty liver disease

Jose L. Flores-Guerrero*, Adrian Post, Peter R. van Dijk, Margery A. Connelly, Erwin Garcia, Gerjan Navis, Stephan J. L. Bakker, Robin P. F. Dullaart

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)
23 Downloads (Pure)

Abstract

Background and Aims Trimethylamine-N-oxide (TMAO), a gut microbiota-liver metabolite, has been associated with cardiometabolic disease. However, whether TMAO is associated with nonalcoholic fatty liver disease (NAFLD) and NAFLD-related health outcomes remains unclear. We aimed to investigate the association of TMAO with NAFLD and to assess the extent to which the association of TMAO with all-cause mortality is dependent on the presence of NAFLD in the general population.

Methods We included 5292 participants enrolled in the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort study. Cox proportional-hazards regression analyses were performed to study the association of TMAO with all-cause mortality in subjects with and without a fatty liver index (FLI) >= 60, which was used as a proxy of NAFLD.

Results During a median follow-up of 8.2 years, 307 subjects died, of whom 133 were classified with NAFLD. TMAO was positively and independently associated with baseline FLI (Std beta 0.08, 95% CI 0.05, 0.11, P < .001). Higher TMAO was associated with increased risk of all-cause mortality in subjects with NAFLD, in crude analysis (hazard ratio [HR] per 1 SD, 2.55, 95% CI 1.60, 4.05, P < .001) and after full adjustment (adjHR 1.90, 95% CI 1.18, 3.04, P = .008). Such an association was not present in subjects without NAFLD (crude HR 1.14, 95% CI 0.81, 1.71, P = .39; adjHR 0.95, 95% CI 0.65, 1.39, P = .78).

Conclusion This prospective study revealed that plasma concentrations of TMAO were associated with all-cause mortality in subjects with NAFLD, independently of traditional risk factors.

Original languageEnglish
Pages (from-to)2371-2382
Number of pages12
JournalLiver International
Volume41
Issue number10
Early online date16-May-2021
DOIs
Publication statusPublished - Oct-2021

Keywords

  • microbiota
  • mortality
  • NAFLD
  • nonalcoholic fatty liver disease
  • TMAO
  • trimethylamine-N-oxide
  • CATALYTIC ACTIVITY CONCENTRATIONS
  • CARDIOVASCULAR-DISEASE
  • GUT MICROBIOTA
  • RISK
  • SERUM
  • 37-DEGREES-C
  • METABOLISM
  • ENZYMES
  • PLASMA

Cite this