Huang Liyan, Zhao Xuemei, Wang Jing, Guan Jingyuan, Huang Boping, Feng Jiayu, Li Xinqing, Zhang Yuhui, Zhang Jian
Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
Key Laboratory of Clinical Research for Cardiovascular Medications, National Health Committee, Beijing, China.
ESC Heart Fail. 2025 Aug;12(4):2518-2527. doi: 10.1002/ehf2.15267. Epub 2025 Mar 17.
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.
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.
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.
肠道微生物群失调已被证明与心力衰竭（HF）的发病机制和进展有关。阻碍肠-心轴的有害影响是一个新趋势。我们的目标是研究肠道微生物群与HF之间的因果关系，以便于未来探索以微生物群为靶点的方法来预防和延缓HF的进展。
采用两样本孟德尔随机化（MR）分析，研究欧洲血统个体中肠道微生物群与HF的因果关联。来自MiBioGen联盟的与196种细菌分类群相关的基因变异用作暴露数据，来自心力衰竭治疗靶点分子流行病学（HERMES）联盟的HF汇总统计数据用作结果数据。应用了五种MR方法，包括逆方差加权法、最大似然法、MR-Egger法、加权中位数法和加权模式法。通过MR Steiger方向性检验来检验工具变量（IVs）的反向因果关系。通过F统计量评估IVs的强度。使用Cochrane's Q检验、MR-Egger回归分析和MR多效性残差和离群值（MR-PRESSO）检验来检测异质性和多效性。采用留一法检验结果的稳定性。发现七种微生物群与HF相关。其中五种与发生HF的较高风险相关，包括嗜硒单胞菌目（优势比[OR]=1.11，P=0.024）、消化球菌科（OR=1.07，P=0.045）、 eligens真杆菌属组（OR=1.14，P=0.022）、氧化还原真杆菌属组（OR=1.12，P=0.011）和黄酮分解菌属（OR=1.14，P=0.012）。厌氧棒状菌属和芽孢杆菌目与较低的HF风险相关（分别为OR=0.90，P=0.014；OR=0.95，P=0.042）。未观察到多效性或异质性的证据。
我们在基因预测水平上确定了七种与HF有因果关系的肠道微生物群。本研究将有助于发现HF潜在的预防和治疗靶点。
