Exploring the Axis of Gut Microbiota‐Inflammatory Cytokine‐Atrial Fibrillation in the Pathogenesis of Atrial Fibrillation

ABSTRACT A relationship may exist between the gut microbiota, inflammatory factors and atrial fibrillation (AF); however, the precise biological mechanisms linking these components remain uncertain.In this study, 211 single‐nucleotide polymorphisms associated with the gut microbiota were collected from the MiBioGen consortium. Summary data for AF were sourced from large‐scale genome‐wide association studies. Two‐step Mendelian randomization (MR) was applied to estimate the possible mediating effect of inflammatory cytokines on the causality between the gut microbiota and AF. MR confirmed the effects of class Lentisphaeria, family Bifidobacteriaceae, family XIII, genus Anaerostipes , genus Howardella , genus Intestinibacter , genus Lachnospiraceae (NK4A136 group), genus Odoribacter , genus Ruminococcus gnavus , order Bifidobacteriales, order Victivallales and phylum Lentisphaerae on AF prevention. Moreover, MR revealed the role of Fms‐related tyrosine kinase 3 ligand, interleukin‐6, interleukin‐7, leukaemia inhibitory factor receptor, sulfotransferase 1A1 and tumour necrosis factor ligand superfamily member 12 in protecting against AF. Fibroblast growth factor 5, interleukin‐2 receptor subunit β, and tumour necrosis factor had a causal effect, increasing AF risk. The mediation exploration indicated that the indirect effect of genus Lachnospiraceae (FCS020 group) (id: 11314) on AF mediated by interleukin‐18 was OR 1.015 (95% confidence interval 1.000–1.037; mediation proportion = 9.494%). This study supplies genetic insights into the potential causal association between the gut microbiota and AF. These causal associations and mediating effects are useful for managing AF through manipulation of the gut microbiota.