Guan Xueqing, Sun Chaonan, Su Jianyao, Sun Zhijun, Cheng Cheng
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Radiation Oncology, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China.
Front Pharmacol. 2025 Apr 1;16:1531384. doi: 10.3389/fphar.2025.1531384. eCollection 2025.
Growing evidence suggesting a connection between the gut microbiome, plasma metabolites, and the development of heart failure (HF). However, the causality of this relationship remains to be fully elucidated.
Utilizing summary statistics from extensive genome-wide association studies (GWAS), we investigated the interplay among the gut microbiome, 1,400 plasma metabolites and heart failure. We conducted bidirectional Mendelian randomization (MR) analyses and MR mediation analysis to discern the causality within these relationships. The inverse variance-weighted (IVW) method served as our primary analytical approach, supported by various MR methods and sensitivity analyses.
We revealed casual relationships between nine microbial groups/pathways and heart failure. Additionally, 15 metabolites exhibited casual links with HF, with eight exerting protective effects. Through two-step MR analysis we also identified the metabolite, Campesterol, mediated the increasing risk from gut microbiota to HF and a metabolite ratio played the converse role.
This investigation has provided robust evidence supporting the causal links between the gut microbiome, plasma metabolites, and heart failure. The findings enhance our comprehension of the role of circulating metabolites and offer significant insights for future etiological research and therapeutic development in heart failure.
越来越多的证据表明肠道微生物群、血浆代谢物与心力衰竭（HF）的发生发展之间存在联系。然而，这种关系的因果性仍有待充分阐明。
利用来自广泛的全基因组关联研究（GWAS）的汇总统计数据，我们研究了肠道微生物群、1400种血浆代谢物与心力衰竭之间的相互作用。我们进行了双向孟德尔随机化（MR）分析和MR中介分析，以识别这些关系中的因果性。逆方差加权（IVW）方法是我们的主要分析方法，并得到了各种MR方法和敏感性分析的支持。
我们揭示了9个微生物组/途径与心力衰竭之间的因果关系。此外，15种代谢物与HF存在因果联系，其中8种具有保护作用。通过两步MR分析，我们还确定了代谢物菜油甾醇介导了肠道微生物群增加HF风险的作用，而一种代谢物比值则起到相反的作用。
本研究提供了有力证据，支持肠道微生物群、血浆代谢物与心力衰竭之间的因果联系。这些发现增强了我们对循环代谢物作用的理解，并为未来心力衰竭的病因学研究和治疗发展提供了重要见解。
