Plasmatic trimethylamine N-oxide and its relation to stroke: A systematic review and dose-response meta-analysis

Background: Elevated circulating concentrations of the gut metabolite, trimethylamine N-oxide (TMAO), were found in patients who experienced stroke. However, it has not been reported whether a high level of TMAO is associated with a significantly increased risk of stroke. This study aimed to review the available scientific evidence about the relationship between TMAO levels and the risk of stroke in a dose-response meta-analysis. Methods: The PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure databases were searched for studies starting from September 1996 to December 2020. Nine studies including 4402 subjects were reviewed in this study. Results: The results of meta-analysis showed that high levels of circulating TMAO were associated with an increased risk of stroke in patients in the random-effects model (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12–2.41; P = 0.047). The OR for the prevalence of stroke increased by 48% per 5-μmol/L increment (OR, 1.05; 95% CI, 1.16–1.78; P < 0.001) and by 132% per 10-μmol/L increment (OR, 2.32; 95% CI, 1.38–3.86; P < 0.001) in circulating TMAO concentration according to the dose-response meta-analysis. Conclusion: There was a significant association between higher plasma TMAO concentrations and the risk of stroke. Further in-depth studies are warranted to validate this interaction and explore potential mechanisms.