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

Figure 1

Gut dysbiosis and its role in atrial fibrillation. F/B: Firmicutes/Bacteroidetes.

Figure 2

Pathological link between gut dysbiosis and atrial fibrillation. AF: Atrial Fibrillation; FGF: Fibroblast growth factor; GPCR: G-protein coupled receptor; GPR: G-protein-coupled receptor; IL: Interleukin; LPS: Lipopolysaccharides; NF-κB: Nuclear factor kappa B; NLRP3: Nod-like receptor protein 3; PAGln Phenylacetylglutamine; SCFA: Short-chain fatty acids; TNF: Tumor necrosis factor; TLR: Toll-like receptor; TMAO: Trimethylamine N-oxide.

Figure 3

Gut modulation-based individualized care in atrial fibrillation. AF: Atrial fibrillation; GPC: G-protein coupled; HF: Heart failure; MI: Myocardial infarction; SCFA: Short-chain fatty acids.