Tan Jiangshan, Wang Jingyang, Yang Yanmin, Zhu Jun, Wang Lulu, Xu Wei, Lyu Siqi, Wu Shuang, Wang Juan, Zhang Han
Emergency and Critical Care Center, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Transl Int Med. 2025 Jun 20;13(3):241-252. doi: 10.1515/jtim-2025-0031. eCollection 2025 Jun.
Considerable evidence has shown that alterations in gut microbiota composition are associated with atrial fibrillation (AF). However, the causal associations remain largely unresolved. This study aims to reveal the causality between gut microbiota and AF.
We incorporated data from the largest genome-wide association studies (GWASs) of gut microbiota composition (involving 18,304 individuals) and GWASs of AF (comprising 60,620 cases and 970,216 controls) in European individuals. A two-sample Mendelian randomization framework was designed to investigate the role of gut microbiota in the development of AF. The inverse variance weighted method was applied for the main causal estimate. Complementary sensitivity analyses were utilized to confirm the robustness of the results. Finally, gene ontology enrichment analyses and Kyoto Encyclopedia of genes and genomes pathway analysis are used to investigate the bio-function.
Among all gut microbiota, five microbial taxa, namely , , , , and were identified to be causally associated with the higher risk of AF. Besides, genetically predicted eight microbial taxa, namely , , , , , , , and can prevent AF.
Our study provides evidence of the causal effect of the gut microbiota on AF, highlighting causal microbial taxa. Our results may offer novel insights into gut microbiota-mediated mechanisms and interventions of AF.
大量证据表明，肠道微生物群组成的改变与心房颤动（AF）有关。然而，因果关系在很大程度上仍未得到解决。本研究旨在揭示肠道微生物群与AF之间的因果关系。
我们纳入了欧洲人群中关于肠道微生物群组成的最大规模全基因组关联研究（GWAS，涉及18304人）以及AF的GWAS（包括60620例病例和970216例对照）的数据。设计了一个两样本孟德尔随机化框架来研究肠道微生物群在AF发生发展中的作用。主要因果估计采用逆方差加权法。采用补充敏感性分析来确认结果的稳健性。最后，利用基因本体富集分析和京都基因与基因组百科全书通路分析来研究生物功能。
在所有肠道微生物群中，确定了5个微生物分类群，即 、 、 、 和 与AF的较高风险存在因果关系。此外，基因预测的8个微生物分类群，即 、 、 、 、 、 、 和 可以预防AF。
我们的研究提供了肠道微生物群对AF有因果作用的证据，突出了因果微生物分类群。我们的结果可能为肠道微生物群介导的AF机制和干预提供新的见解。
