The gut-heart axis in atrial fibrillation: Pathophysiology, evidence, and therapeutic potential

Recent advances in microbiome research highlight a bidirectional relationship between gut microbiota and atrial fibrillation (AF), the most common sustained arrhythmia worldwide. Gut dysbiosis has been implicated in systemic inflammation, metabolite imbalance, bile acid signaling, and autonomic dysfunction, whereas AF itself alters microbial homeostasis through hemodynamic and neurohormonal changes.

This review aimed to synthesize current evidence linking gut dysbiosis to AF pathogenesis, identify mechanisms underlying this interaction, and explore the therapeutic potential of microbiota-targeted interventions.

We conducted a narrative review of preclinical, clinical, and epidemiologic studies examining the gut-heart axis in AF. Particular emphasis was placed on microbial metabolites (eg, trimethylamine N-oxide, short-chain fatty acids, indoxyl sulfate), bile acid modulation, and inflammatory signaling. Data on interventions, including diet, probiotics, pharmacologic approaches, and fecal microbiota transplantation, were integrated to assess translational potential.

Evidence suggests that gut-derived signals contribute to atrial remodeling through activation of the NLRP3 inflammasome, altered calcium handling, and impaired gap junction integrity. Conversely, AF promotes dysbiosis by reducing gut perfusion, altering motility, and exposing patients to polypharmacy. Microbiota-directed strategies, particularly dietary modification and probiotics, demonstrate promise in reducing arrhythmic risk, whereas early data indicate potential biomarker roles for gut microbial signatures in AF stratification. However, causality remains uncertain, given that most studies are observational with limited sample sizes.

The gut-heart axis represents a novel paradigm in AF research. Although preliminary findings support its mechanistic and therapeutic relevance, interventional studies are needed to establish causality and guide clinical application.