Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian
BackgroundGrowing 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.MethodsUtilizing summary statistics from extensive genome-wide association studies...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1531384/full |
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| author | Xueqing Guan Chaonan Sun Jianyao Su Zhijun Sun Cheng Cheng |
| author_facet | Xueqing Guan Chaonan Sun Jianyao Su Zhijun Sun Cheng Cheng |
| author_sort | Xueqing Guan |
| collection | DOAJ |
| description | BackgroundGrowing 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.MethodsUtilizing 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.ResultsWe 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.ConclusionThis 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. |
| format | Article |
| id | doaj-art-ed4e5348a1fc4ea2ba4c5202b2428c09 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-ed4e5348a1fc4ea2ba4c5202b2428c092025-08-20T01:50:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15313841531384Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelianXueqing Guan0Chaonan Sun1Jianyao Su2Zhijun Sun3Cheng Cheng4Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, ChinaDepartment of Cardiology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Cardiology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Cardiology, Shengjing Hospital of China Medical University, Shenyang, ChinaBackgroundGrowing 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.MethodsUtilizing 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.ResultsWe 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1531384/fullcirculating metabolitesheart failuremendelian randomizationmicrobiotasingle-cell sequencing |
| spellingShingle | Xueqing Guan Chaonan Sun Jianyao Su Zhijun Sun Cheng Cheng Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian Frontiers in Pharmacology circulating metabolites heart failure mendelian randomization microbiota single-cell sequencing |
| title | Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian |
| title_full | Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian |
| title_fullStr | Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian |
| title_full_unstemmed | Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian |
| title_short | Deciphering the causality of gut microbiota, circulating metabolites and heart failure: a mediation mendelian |
| title_sort | deciphering the causality of gut microbiota circulating metabolites and heart failure a mediation mendelian |
| topic | circulating metabolites heart failure mendelian randomization microbiota single-cell sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1531384/full |
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