A systematic review and meta-analysis of the gut microbiota-dependent metabolite trimethylamine N-oxide with the incidence of atrial fibrillation

Background: The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized as one of the novel marker for adverse cardiovascular events and risk of death. However, data on the relationship between TMAO and atrial fibrillation (AF) is limited. The current study was performed to quantify and evaluate the relationship between circulating TMAO levels and AF occurrence. Methods: The electronic databases PubMed, Cochrane Library, and Embase were systematically searched to March 20, 2021. Research studies were considered that recorded or analyzed the prevalence of AF in individuals in specific populations as well as their circulating TMAO levels. A meta-analysis of two-class variables was used to obtain pooled effects. A dose-response meta-analysis was used to investigate the doseresponse relationship between TMAO levels and the risk of AF. Results: Six studies with a total of 8,837 individuals and 1,668 AF cases were included in the present metaanalysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher prevalence of AF [odds ratio (OR): 1.40; 95% confidence interval (CI): 1.23, 1.59; I-2=19.8%]. The doseresponse analysis revealed the risk of AF increased by 6% per 1-mu mol/L increment (OR: 1.06; 95% CI: 1.00, 1.11), 32% per 5-mu mol/L increment (OR: 1.32; 95% CI: 1.03, 1.70), and 73% per 10-mu mol/L increment (OR: 1.73; 95% CI: 1.05, 2.86) of the circulating TMAO level. Discussion: This is the first systematic literature review and meta-analysis to demonstrate a significant dose-dependent relationship between increased AF risk and circulating TMAO levels.