Abstract
BACKGROUND AND OBJECTIVES: Considerable evidence has shown that alterations in gut microbiota composition are associated with atrial fibrillation (AF). However, the causal associations remain largely unresolved. This study aims to reveal the causality between gut microbiota and AF. METHODS: We incorporated data from the largest genome-wide association studies (GWASs) of gut microbiota composition (involving 18,304 individuals) and GWASs of AF (comprising 60,620 cases and 970,216 controls) in European individuals. A two-sample Mendelian randomization framework was designed to investigate the role of gut microbiota in the development of AF. The inverse variance weighted method was applied for the main causal estimate. Complementary sensitivity analyses were utilized to confirm the robustness of the results. Finally, gene ontology enrichment analyses and Kyoto Encyclopedia of genes and genomes pathway analysis are used to investigate the bio-function. RESULTS: Among all gut microbiota, five microbial taxa, namely Lachnospiraceae FCS020, Rikenellaceae RC9 gut group, Catenibacterium, Victivallis, and Erysipelatoclostridium were identified to be causally associated with the higher risk of AF. Besides, genetically predicted eight microbial taxa, namely Lachnospiraceae NK4A136 group, Howardella, Intestinibacter bartlettii, Alloprevotella, Anaerostipes, Odoribacter, Ruminococcus (gnavus group), and Ruminiclostridium 5 can prevent AF. CONCLUSION: Our study provides evidence of the causal effect of the gut microbiota on AF, highlighting causal microbial taxa. Our results may offer novel insights into gut microbiota-mediated mechanisms and interventions of AF.