Due to the increasing prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), it has become a global health challenge by being the most common cause of chronic liver disease. Recently, the microbiota has been linked to NAFLD, via altered bile acid and lipid metabolism. Whether serum Trimethylamine-N-oxide (TMAO), a gut microbiota-dependent metabolite, is associated with NAFLD and NAFLD health outcomes remains unclear. The aim was 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.
We included 6415 participants enrolled in the PREVEND (Prevention of Renal and Vascular End-stage Disease) general population-based cohort study. TMAO was measured by Nuclear Magnetic Resonance Spectroscopy. Cox proportional-hazards regression analyses, adjusted for traditional risk factors, were performed to study the association of TMAO with all-cause mortality in subjects with and without NAFLD, determined by Fatty Liver Index (FLI) ≥ 60.
A total of 3694 had a FLI score < 60, and 1598 ≥ 60. During a median follow-up of 8.2 years, 307 participants died, of whom 133 were classified with NAFLD. TMAO concentrations were positively associated with FLI at baseline (Std β 0.08, 95% CI 0.05; 0.11, P < 0.001). Cox regression analyses revealed that TMAO was associated with increased risk of all-cause mortality in crude analysis (Hazard Ratio (HR), 2.55, 95% CI 1.60, 4.05, P < 0.001) and after full adjustment for age, sex, blood pressure, smoking status, alcohol consumption, cancer history, type 2 diabetes, use of lipid lowering medication, total cholesterol, HDL-cholesterol, glucose, albuminuria and eGFR (adjHR 1.90, 95% CI 1.18, 3.04, P = 0.008), in subjects with NAFLD. Such an association was not present in subjects without NAFLD, neither in the crude model (HR 1.14, 95% CI 0.81, 1.71, P = 0.39), nor in the fully adjusted model (adjHR 0.95, 95% CI 0.65, 1.39, P = 0.78).
This prospective study revealed that plasma concentrations of TMAO were associated with all-cause mortality in subjects with NAFLD independently of traditional risk factors.
22 May 2021 - 26 May 2021