Bidirectional Mendelian randomization study on the association between gut microbiota and atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia requiring lifelong treatment. While the gut microbiota has been linked to several cardiovascular diseases, its direct causal relationship with AF remains unclear, and the underlying "gut-heart" axis hypothesis requires validation. This study aimed to explore the bidirectional association between gut microbial profiles and the risk of AF to clarify this potential etiologic pathway. Genetic summary statistics of gut microbiota and AF were obtained from MiBioGen consortium and FinnGen cohort, respectively. Bidirectional Mendelian randomization (MR) analysis was used to assess the causality. Inverse-variance weighted (IVW) MR was the main approach to generate the estimates, and a series of sensitivity analyses were performed to examine the robustness of results. The forward MR analysis identified 12 bacterial taxa associated with AF risk; specifically, Coprococcus (OR: 1.22; 95% CI: 1.05-1.41; P = .008) was positively associated with AF, whereas, Holdemania (OR: 0.87; 95% CI: 0.78-0.97; P = .011) and Alphaproteobacteria (OR: 0.85; 95% CI: 0.74-0.97; P = .013) were inversely associated with the risk. Reverse MR analysis found that the diagnosis of AF was related to the abundance of 17 bacterial genera, such as Coprococcus (OR: 1.06; 95% CI: 1.03-1.10; P = .001), Ruminococcus gnavus group (OR: 1.09; 95% CI: 1.03-1.16; P = .002), Erysipelotrichia (OR: 1.05; 95% CI: 1.02-1.09; P = .003) and so on. Bidirectional association was found between Coprococcus or Lachnospiraceae and AF. In this study, MR analysis showed that there was a potential mutually causality between gut microbiota and the risk of AF, which may provide new insights for further studies of the role of gut microbiota in AF pathophysiology and development.