Gut, microbiota-dependent trimethylamine-N-oxide is associated with long-term all-cause mortality in patients with exacerbated chronic obstructive pulmonary disease

Objectives: The gut, microflora-dependent metabolite trimethylamine-N-oxide (TMAO) has emerged as a dietary-associated risk factor for incident cardiovascular events. Chronic obstructive pulmonary disease (COPD) is a prevalent disease worldwide with a high associated risk for cardiovascular disease and death due to an infectious cause.

Aims: To study whether TMAO is predictive for adverse clinical outcomes in patients with exacerbated COPD.

Methods: A total of 189 patients with COPD exacerbation were prospectively followed for a median of 6.1 y. TMAO plasma levels at the time of emergency department admission were measured by liquid chromatography coupled with tandem mass spectrometry. Cox and linear regression models were used to investigate associations of TMAO with all-cause mortality and different comorbidities.

Results: All-cause mortality was 55.6% after 6 y. The deceased patients showed significantly higher median admission TMAO (μmol/L) levels compared with survivors (3.9 [interquartile range: 2.3-7.1] versus 2.9 [interquartile range: 1.8-4.7]; P = 0.01), which resulted in an unadjusted hazard ratio of 1.8 ([95% confidence interval: 1.2-3.0], P = 0.01). This association was no longer significant after multivariate adjustment. Median TMAO levels were similar in nonpneumonic and pneumonic COPD exacerbation. Higher age, higher body mass index, diabetes mellitus, and chronic kidney disease were predictors for increased plasma TMAO levels in linear regression analysis.

Conclusions: Increased circulating TMAO levels per se were associated with long-term all-cause mortality in patients with COPD independent of type of exacerbation. However, this association was largely explained by comorbidities and age. Whether TMAO levels can additionally be influenced by nutritional interventions should be addressed in future studies.