Significant correlation between the gut microbiota-derived metabolite trimethylamine-N-oxide and the risk of stroke: evidence based on 23 observational studies.

The gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is regarded as a major risk factor for cardiovascular events and diabetes. However, the association of TMAO with stroke has yet to be fully elucidated. The present meta-analysis was conducted to explore the association between TMAO and stroke. The present meta-analysis quantitatively summarized the results of studies that investigated the association between TMAO and stroke. The PubMed, Embase, Cochrane Library and Web of Science databases were systematically searched from January 1, 2001 to June 1, 2021. All studies that evaluated the association between TMAO and stroke were included in the present systematic review. The present meta-analysis included 30,808 participants and revealed that being in the higher TMAO category increased the odds of stroke by 68% (OR 1.83; 95% CI 1.02-3.29; P = 0.04), and that the mean TMAO concentration in stroke patients was 2.20 μmol/L higher than that of non-stroke controls (MD 2.20; 95% CI 1.23-3.16; P < 0.00001). In addition, TMAO plasma levels was associated with the risk of all-cause mortality, with a pooled HR of 1.89 (95% CI 1.15-3.08; P = 0.01). Both univariate analysis (UVA) and multivariate analysis (MVA) indicated that high TMAO levels significantly increased the risk of major adverse cardiovascular events (MACEs), with pooled RRs of 2.26 (95% CI 2.01-2.54; P < 0.00001) with UVA and 1.55 (95% CI 1.17-2.05; P = 0.002) with MVA respectively. In the current meta-analysis we revealed the positive association between circulating TMAO and stroke. Higher TMAO levels increased the risk of stroke and stroke patients experienced higher mean TMAO concentration. In addition, high TMAO plasma level was one of independent risk factors of MACEs and was associated with all-cause mortality.