Gut microbiome and atrial fibrillation: mechanistic insights metabolites and comorbidities. Systematic review

Emerging evidence indicates that the gut microbiome (GM) and its metabolites may play a role in the development of cardiometabolic diseases, including atrial fibrillation (AF). Although the current data are limited, studies suggest that the GM composition in AF mirrors that observed in associated conditions such as heart failure, hypertension, diabetes, and coronary artery disease (characterized by increased genera <i>Lactobacillus, Enterococcus, Streptococcus</i>, and decreased genus <i>Faecalibacterium</i>). Additionally, patients with AF appear to have distinct microbial alterations, including increased abundances of the genera <i>Dialister, Dorea, Haemophilus, Klebsiella, Lachnospira, Parabacteroides, Ruminococcus</i>, and <i>Veillonella</i> and decreased abundances of the genera <i>Butyricicoccus, Hungatella</i>, and <i>Prevotella</i>. Gut-derived metabolites also show associations with AF. Trimethylamine <i>N</i>-oxide and choline have been linked to new-onset and postoperative AF, potentially via autonomic, inflammatory, and fibrotic pathways. In contrast, short-chain fatty acids, which are reduced in AF patients, may offer protective effects. Elevated lipopolysaccharide levels are correlated with AF onset and recurrence through inflammation and structural remodeling. Indoxyl sulfate and bile acids may contribute to arrhythmogenesis via oxidative stress, apoptosis, and disrupted calcium signaling. These mechanisms contribute to AF by disrupting conduction and increasing automaticity. Emerging evidence also links gut microbes to other arrhythmias, but more research is needed to clarify causality and therapeutic potential.