Gut microbiota and risk of heart failure in European population—A comprehensive Mendelian randomization study

IF 3.7 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS ESC Heart Failure Pub Date : 2025-03-17 DOI:10.1002/ehf2.15267

Liyan Huang, Xuemei Zhao, Jing Wang, Jingyuan Guan, Boping Huang, Jiayu Feng, Xinqing Li, Yuhui Zhang, Jian Zhang

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Abstract

Aims

Gut dysbiosis is proven to be involved in the pathogenesis and progression of heart failure (HF). Hindering the detrimental effects of gut-heart axis is an emerging trend. Our goal is to investigate the causal relationship between gut microbiota and HF, with the aim of facilitating future exploration of microbiome-targeted approaches to prevent and delay the progression of HF.

Methods and results

Two-sample Mendelian randomization (MR) analysis was applied to investigate the causal association of the gut microbiome with HF among individuals of European ancestry. Genetic variants associated with the 196 bacterial taxa from MiBioGen consortium were used as exposure data, summary statistics for HF derived from Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) consortium were used as outcome data. Five MR methods were applied, including inverse variance weighted, maximum likelihood, MR-Egger, weighted median, and weighted mode. Reverse causality of instrumental variables (IVs) was tested by MR Steiger test of directionality. Strength of IVs was evaluated by F-statistics. Cochrane's Q test, MR-Egger regression analysis, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) tests were used to detect heterogeneity and pleiotropy. Leave-one-out method was used for testing the stability of results. Seven microbiomes were found to be associated with HF. Five of them were associated with higher risks of developing HF, these included Order_Selenomonadales (odds ratio [OR] = 1.11, P = 0.024), Family_Peptococcaceae (OR = 1.07, P = 0.045), Genus_Eubacterium eligens group (OR = 1.14, P = 0.022), Genus_Eubacterium oxidoreducens group (OR = 1.12, P = 0.011) and Genus_Flavonifractor (OR = 1.14, P = 0.012). Genus_Anaerostipes and Order_Bacillales were associated with lower risks of HF (OR = 0.90, P = 0.014; OR = 0.95, P = 0.042, respectively). Evidence of pleiotropy or heterogeneity was not observed.

Conclusions

We identified seven intestinal microbiomes that were causally associated with HF at the level of gene prediction. This study will help with the discovery of potential preventive and therapeutic targets for HF.

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欧洲人群的肠道菌群和心力衰竭的风险——一项全面的孟德尔随机研究。

目的：肠道生态失调被证实参与心力衰竭（HF）的发病和进展。阻碍肠心轴的有害影响是一个新兴的趋势。我们的目标是研究肠道微生物群与HF之间的因果关系，以促进未来探索以微生物群为目标的方法来预防和延缓HF的进展。方法和结果：采用双样本孟德尔随机化（MR）分析，研究欧洲血统人群中肠道微生物组与HF的因果关系。来自MiBioGen联盟的196个细菌分类群相关的遗传变异作为暴露数据，来自心力衰竭治疗靶点分子流行病学（HERMES）联盟的HF汇总统计数据作为结局数据。应用了五种MR方法，包括方差反加权、最大似然、MR- egger、加权中位数和加权模式。用MR Steiger方向性检验检验工具变量的反向因果关系。采用f统计法评价静脉注射的强度。采用Cochrane’s Q检验、MR- egger回归分析和MR多效性残差和异常值（MR- presso）检验检测异质性和多效性。采用留一法检验结果的稳定性。七个微生物组被发现与HF相关。其中5个与HF发生高风险相关，包括Order_Selenomonadales（比值比[OR] = 1.11, P = 0.024）、Family_Peptococcaceae（比值比[OR] = 1.07, P = 0.045）、Genus_Eubacterium eligens组（比值比= 1.14,P = 0.022）、Genus_Eubacterium oxidoreducens组（比值比= 1.12,P = 0.011）和genus_flavonoids ifractor组（比值比= 1.14,P = 0.012）。genus_anaerosties和Order_Bacillales与HF风险较低相关(OR = 0.90, P = 0.014；OR = 0.95, P = 0.042)。没有观察到多效性或异质性的证据。结论：我们在基因预测水平上确定了7个与HF有因果关系的肠道微生物组。这项研究将有助于发现心衰的潜在预防和治疗靶点。

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来源期刊

ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine

CiteScore

7.00

自引率

7.90%

发文量

461

审稿时长

12 weeks

期刊介绍： ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.