Abstract

Dysbiotic gut microbiota (GM) and disordered metabolic patterns are known to be involved in the clinical expression of atrial fibrillation (AF). However, little evidence has been reported in characterizing the specific changes in fecal microbiota in paroxysmal AF (PAF) and persistent AF (psAF). To provide a comprehensive understanding of GM dysbiosis in AF types, we assessed the GM signatures of 30 PAF patients, 20 psAF patients, and 50 non-AF controls based on metagenomic and metabolomic analyses. Compared with control subjects, similar changes of GM were identified in PAF and psAF patients, with elevated microbial diversity and similar alteration in the microbiota composition. PAF and psAF patients shared the majority of differential taxa compared with non-AF controls. Moreover, the similarity was also illuminated in microbial function and associated metabolic alterations. Additionally, minor disparity was observed in PAF compared with psAF. Several distinctive taxa between PAF and psAF were correlated with certain metabolites and atrial diameter, which might play a role in the pathogenesis of atrial remodeling. Our findings characterized the presence of many common features in GM shared by PAF and psAF, which occurred at the self-terminating PAF. Preventative and therapeutic measures targeting GM for early intervention to postpone the progression of AF are highly warranted.IMPORTANCE Atrial fibrillation has been identified to be associated with disordered gut microbiota. Notably, atrial fibrillation is a progressive disease and could be categorized as paroxysmal and persistent based on the duration of the episodes. The persistent atrial fibrillation patients are accompanied by higher risk of stroke and lower success rate of rhythm control. However, the microbial signatures of different categories of atrial fibrillation patients remain unknown. We sought to determine whether disordered gut microbiota occurs in the self-terminating PAF or intestinal flora develops dynamically during atrial fibrillation progression. We found that different types of atrial fibrillation show a limited degree of gut microbiota shift. Gut microbiota dysbiosis has already occurred in mild stages of atrial fibrillation, which might act as an early modulator of disease, and therefore may be regarded as a potential target to postpone atrial fibrillation progression.

Highlights

  • Dysbiotic gut microbiota (GM) and disordered metabolic patterns are known to be involved in the clinical expression of atrial fibrillation (AF)

  • To provide a comprehensive understanding of GM dysbiosis in the development of AF, we analyzed the GM and metabolic features in paroxysmal AF (PAF) and persistent AF (psAF) patients based on high-throughput metagenomic and metabolomic analyses

  • The results showed that AF was associated with increased microbial gene number, Shannon index, Pielou evenness, Chao richness, altered principal-component analysis (PCA), principal-coordinate analysis (PCoA), nonmetric dimensional scaling (NMDS) index, and Firmicutes/Bacteroidetes (F/B) ratio as well as higher abundance of Firmicutes and lower abundance of Bacteroidetes independent of age, body mass index (BMI), HTN, or type 2 diabetes mellitus (T2DM) (Table S2)

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Summary

Introduction

Dysbiotic gut microbiota (GM) and disordered metabolic patterns are known to be involved in the clinical expression of atrial fibrillation (AF). We sought to determine whether disordered gut microbiota occurs in the self-terminating PAF or intestinal flora develops dynamically during atrial fibrillation progression. Gut microbiota dysbiosis has already occurred in mild stages of atrial fibrillation, which might act as an early modulator of disease, and may be regarded as a potential target to postpone atrial fibrillation progression. Whether disordered GM occurs in the self-terminating PAF or intestinal flora develops dynamically during AF progression remains to be explored. These seminal issues encouraged us to identify the patterns of GM in PAF and psAF. To provide a comprehensive understanding of GM dysbiosis in the development of AF, we analyzed the GM and metabolic features in PAF and psAF patients based on high-throughput metagenomic and metabolomic analyses. Our study reveals that alterations of GM occur at a mild stage of AF, and the manipulation of targeted GM should focus on early prevention of AF in the future

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