Gut microbial metabolite TMAO portends prognosis in acute ischemic stroke.

BACKGROUND

Over the recent years, the role of trimethylamine N-oxide (TMAO) as a gut-derived metabolite mediating cardiovascular disease pathogenesis has been under particularly intense scrutiny. The aim was to explore whether TMAO levels were associated with clinical severity or functional outcome in Chinese patients with ischemic stroke.

METHODS

This is a single-center, prospective cohort study from Xiamen, China. We examined the relationship between fasting TMAO and 2 of its nutrient precursors, choline and betaine, vs. 3-month functional outcome and mortality in 351 first-ever patients with acute ischemic stroke.

RESULTS

The median value of the plasma level of TMAO was 6.1 μM (IQR, 3.7-9.9 μM), which was higher than in those control cases (4.0; 2.4-5.9 μM). Patients with a poor outcome and nonsurvivors had significantly increased TMAO levels on admission (P < 0.001). Following adjustments for traditional risk factors, increased TMAO concentrations remained predictive of both poor outcome and mortality risks in stroke patients [e.g., quartiles 4 vs 1, odd ratio 5.65 (95% CI, 2.87-13.45), P < 0.001; and 5.84 (95% CI, 3.05-16.12), P < 0.001, respectively]. In multivariate analysis, TMAO was an independent predictor of functional outcome and mortality and improved the prognostic accuracy of the NIHSS to predict functional outcome (combined areas under the curve, 0.82; 95% CI 0.77-0.89, P = 0.003) and mortality (combined areas under the curve, 0.85; 95% CI: 0.80-0.90, P = 0.002).

CONCLUSIONS

Fasting plasma concentrations of gut microbial TMAO are higher in patients with ischemic stroke and portend higher poor functional outcome events and mortality.