Abstract
Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of “gut-immune-heart” axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.
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Background
From the results of physiological, epidemiological, and omics-based studies, complemented by cellular and animal experiments, microbial communities might coordinate or modify a significant portion of environmental impacts on human health [1,141]. Prior observational investigation has upheld the connection between periodontitis and AF irrespective of known confounders [142]. In an animal model, periodontitis has been observed to strengthen the immune activation of the atrial myocardium, thereby subverting the electrophysiological properties of the atria [143]. A recent population-based cohort study of 161,286 subjects revealed that improvements in oral hygiene such as regular professional dental cleanings and frequent tooth brushing were linked to a decreased risk of AF [144]. However, few experiments have been conducted to study the role and mechanisms of oral flora in AF pathophysiology. Future investigations may benefit from interrogating the connection between the characteristics as well as the metabolism of oral flora and AF. Considering the treatment of periodontitis as a highly feasible and daily manageable measure for AF prevention, randomized clinical trials dealing with standardized oral flora interventions are warranted to demonstrate the advantage of periodontal treatment in mitigating AF risk.
Because of the heterogeneity and transparency of the gut microbiome as well as state-of-the-art technological advances, meta-omics approaches hold a prospect as a gateway to unveiling host-microbiome interactions and evaluating causality in the clinical milieu. Nevertheless, it has restrictions and requires further innovation. A portion of the data could not be allotted on account of insufficient reference databases, especially the scarcity of eukaryotic and viral matches, which hampered the extraction of organismal and functional information. Currently, only the bacterial community has been extensively studied, whilst other constituents of the gut microbiota, such as viruses, fungi, or archaea, have not been prolifically explored. Zuo et al. [38] have demonstrated that enterovirus features were correlated with AF for the first time, which has tremendous potential value in anticipating ablation outcomes (Table 1). Therefore, the conjunction of these members in microbial-AF association analysis may unlock a fresh door for potential therapeutic approaches. Furthermore, another difficulty of special pertinence to microbiome studies is the drastic inter-individual variation in the configuration of the gut microbiome and the subsequent host metabolism induced by dietary interventions. In turn, applying machine learning to datasets encompassing diet, gut flora, and genetics might deliver the solution. Apart from direct causal routes, specific bacteria or microbiota constituents may be implied by incident or simply as modifying variables in drug regimens and genetic studies. Thus, the microbiome remains a crucial segment of personalized and precision medicine.
Availability of data and materials
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Abbreviations
- AF:
-
Atrial fibrillation
- ANS:
-
Autonomic nervous system
- BAs:
-
Bile acids
- CaMKII:
-
Calmodulin kinase II
- CASP1:
-
Caspase-1
- CFs:
-
Cardiac fibroblasts
- CMs:
-
Cardiac myocytes
- Cx:
-
Connexin
- DAMPs:
-
Damage-associated molecular patterns
- DMB:
-
Dimethylbutanol
- FMT:
-
Fecal microbiota transplantation
- GPR43:
-
G protein-coupled receptor 43
- IL:
-
Interleukin
- LPS:
-
Lipopolysaccharides
- miRNAs or miRs:
-
MicroRNAs
- NF-κB:
-
Nuclear factor-κB
- NLRP3:
-
NACHT, LRR, and PYD domains-containing protein-3
- OACs:
-
Oral anticoagulants
- PAGln:
-
Phenylacetylglutamine
- PAMPs:
-
Pathogen-associated molecular patterns
- PRRs:
-
Pattern recognition receptors
- ROS:
-
Reactive oxygen species
- RyR2:
-
Ryanodine receptor 2
- SCFAs:
-
Short-chain fatty acids
- TGF-β:
-
Transforming growth factor-β
- TMA:
-
Trimethylamine
- TMAO:
-
Trimethylamine oxide
- TNF:
-
Tumor necrosis factor
- TLR:
-
Toll-like receptor
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This study was sponsored by Grants from the National Key Research and Development Program of China (2022YFC2303100), the Central Plains Talent Program-Central Plains Youth Top Talents, the Young and Middle-aged Academic Leaders of Henan Provincial Health Commission (HNSWJW-2022013), the Funding for Scientific Research and Innovation Team of the First Affiliated Hospital of Zhengzhou University (QNCXTD2023002 and ZYCXTD2023002), and the Research Project of **an Microecological Biomedicine Shandong Laboratory (JNL-2022001A and JNL-2022015B).
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ZGR, ZJY, and YQY provided direction and guidance throughout the preparation of this manuscript. NL wrote the manuscript. LW, LL, and MZY edited the manuscript, drew the figures, and made significant revisions to the manuscript. QXW, XWB, and FG collected and prepared the related papers. All authors read and approved the final manuscript.
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Li, N., Wang, L., Li, L. et al. The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives. Military Med Res 10, 51 (2023). https://doi.org/10.1186/s40779-023-00489-1
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DOI: https://doi.org/10.1186/s40779-023-00489-1