Duration of Persistent Atrial Fibrillation Is Associated with Alterations in Human Gut Microbiota and Metabolic Phenotypes

Atrial fibrillation (AF) has been shown to be associated with disordered gut microbiota (GM). The underlying factors governing persistent AF (psAF) are not well understood, and the association between AF duration and GM profiles remains to be characterized. Thus, the present study aimed at investigating the dysbiosis of GM in patients with short and long psAF duration and illuminating the relationship between the GM and psAF maintenance. Based on metagenomic sequencing and metabolomic analyses, we assessed the metabolic and GM signature in 12 patients with psAF of <12 months (Pers<12m), eight patients with psAF of >12 months (Pers>12m), and 20 controls. We found that the GM in patients with both Pers<12m and Pers>12m was significantly perturbed, with an elevated microbial diversity, distinct structure, and discrepant composition. Although Pers<12m and Pers>12m patients shared a large number of common bacteria with controls, including 84 genera and 404 species, certain bacteria were differently enriched at different AF durations. Furthermore, disturbance in gut microbial function and GM-linked metabolic alterations were detected in both the Pers<12m and Pers>12m groups. The connection of GM and metabolites with psAF is consistent with interaction and potential modulation of host metabolic pathways due to GM dysbiosis with AF persistence. Our results showed that patients of the Pers<12m and Pers>12m groups shared many common disordered GM and metabolic features, which might occur in early disease, while prolonged psAF duration was related to certain unique alterations. Preventative strategies targeting GM and microbial metabolites for early intervention to treat AF patients are highly warranted. IMPORTANCE Atrial fibrillation was associated with a disordered gut microbiota in previous research. However, the gut microbiota signature of patients at different stages of atrial fibrillation remains largely unknown. We sought to determine whether the shift in the gut microbiota and metabolic profiles occurs early and remains stable or develops gradually during atrial fibrillation. We found that patients with persistent atrial fibrillation of <12 months and persistent atrial fibrillation of >12 months shared most of the common features of gut microbiota dysbiosis. However, some distinctive and progressive alterations in the gut microbiota and metabolic structure, which may contribute to the progression of atrial fibrillation, were identified. The present study provides a comprehensive description of the dysbiotic gut microbiota and metabolic profiles in patients of short and long persistent atrial fibrillation, and our findings may help identify therapeutic strategies targeting the gut microbiota to treat atrial fibrillation at an early stage.