Impact of gut microbiome on atrial fibrillation: Mechanistic insights and future directions in individualized medicine

Abstract

Atrial fibrillation (AF) is a growing global health burden, with a prevalence of over 52.55 million cases. Rising disability-adjusted life-years, increasing age, and disparities in care have contributed to the worsening severity and mortality of AF. Modifiable risk factors, such as hypertension, obesity, and diabetes mellitus, are associated with alterations in gut microbiota, making the gut-heart axis a potential therapeutic target. Gut dysbiosis influences AF pathogenesis through inflammation, metabolic disruption, and autonomic dysfunction. Key mechanisms include gut barrier dysfunction, short-chain fatty acid (SCFA) depletion, lipopolysaccharides (LPS)-induced inflammation, and ferroptosis-mediated atrial remodeling. Trimethylamine N-oxide, bile acids, and tryptophan metabolites contribute to arrhythmogenic remodeling. Emerging evidence suggests that dietary interventions, including prebiotics and probiotics, as well as gut surveillance, may help mitigate AF progression. Clinical implications of gut modulation in AF include personalized dietary strategies, microbiome assessment through metagenomic sequencing, and targeted interventions such as SCFA-based therapies and ferroptosis inhibition. Metabolite surveillance, including LPS and indoxyl sulfate monitoring, may influence the effectiveness of anticoagulant and antiarrhythmic therapy. Despite growing mechanistic evidence linking gut dysbiosis to AF, clinical applications remain unexplored. This review summarizes the current understanding of the gut microbiome's role in AF.

Keywords: Atrial fibrillation; Gut microbiome; Dysbiosis; Inflammation; Short-chain-fatty-acid; Trimethylamine N-oxide; Ferroptosis; Lipopolysaccharides; Microbiome-based therapy; Individualized care

Core Tip: Gut microbiome alteration contributes to the generation of harmful metabolites, loss of gut integrity, and cardiac remodeling. Gut dysbiosis interacts with modifiable risk factors to promote cardiac tissue remodeling. Animal models and clinical studies indicate that microbial composition is associated with arrhythmogenesis, atrial fibrillation (AF) recurrence, and modulates medication response. Integrating microbiome surveillance and gut microbiome modulation therapy into AF management may slow disease progression and reduce the arrhythmia burden. However, clinical trials are needed to establish causality and support the incorporation of gut modulation into clinical care.