Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study
Background Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the pot...
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Taylor & Francis Group
2024-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10641963.2024.2390419 |
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| author | Chaozhong Li Zhengqing Liu Siqian Yang Wanrong Li Bo Liang Haoyu Chen Yujia Ye Fang Wang Xiaoqing Liu Yongliang Jiang Haiying Wu Yunzhu Peng Zhaohui Meng |
| author_facet | Chaozhong Li Zhengqing Liu Siqian Yang Wanrong Li Bo Liang Haoyu Chen Yujia Ye Fang Wang Xiaoqing Liu Yongliang Jiang Haiying Wu Yunzhu Peng Zhaohui Meng |
| author_sort | Chaozhong Li |
| collection | DOAJ |
| description | Background Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the potential causal relationships involving gut microbiota-mediated plasma metabolites, inflammatory cytokines, and AAA.Methods We utilized data from genome-wide association studies predominantly comprising individuals of European ancestry, encompassing four major gut microbiota signatures, 233 plasma metabolite signatures (N = 136,016), 91 inflammatory cytokine signatures (N = 14,824), and AAA signatures (N = 1,458,875). Mendelian randomization (MR), employed in a two-sample format, was utilized as a tool to investigate the potential causal pathways from gut microbiota to the development of AAA. Additionally, a two-step MR approach was employed to dissect the impact of plasma metabolites and inflammatory cytokines on the relationship between gut microbiota and AAA and to ascertain the mediated fractions.Results Our findings indicate that five phylum or family-identical bacteria, 175 plasma metabolites, and seven inflammatory factors are causally associated with AAA. Among them, five bacterial species from the same phylum or family, identified from different GWAS data, were strongly associated with AAA. Of these, two exhibited negative causality and three exhibited positive causality. We found that the phylum Firmicutes and the families Oscillospiraceae might reduce the risk of AAA, whereas the families Prevotellaceae, Sutterellaceae, and Aminobacteriaceae might increase the risk of AAA. Further screening indicated that phylum Firmicutes id.1672 (GCST90017114) may confer a protective effect against AAA by reducing triglyceride levels in medium/small high-density lipoprotein (HDL).Conclusion MR analysis has delineated a causal pathway from gut microbiota, through plasma circulating metabolites and inflammatory cytokines, to the pathogenesis of AAA. The role of intestinal flora and certain biomarkers may provide a reference for the diagnosis of AAA, and contribute to the prevention, diagnosis, and treatment of AAA disease. |
| format | Article |
| id | doaj-art-a39a736e19ec473e8efee6b28528f5f0 |
| institution | DOAJ |
| issn | 1064-1963 1525-6006 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Clinical and Experimental Hypertension |
| spelling | doaj-art-a39a736e19ec473e8efee6b28528f5f02025-08-20T02:49:05ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062024-12-0146110.1080/10641963.2024.2390419Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization studyChaozhong Li0Zhengqing Liu1Siqian Yang2Wanrong Li3Bo Liang4Haoyu Chen5Yujia Ye6Fang Wang7Xiaoqing Liu8Yongliang Jiang9Haiying Wu10Yunzhu Peng11Zhaohui Meng12Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Intensive Care Unit, The People’s Hospital of Yunnan Chuxiong Yi Autonomous Prefecture, Chuxiong, ChinaDepartment of Gynecology, Sheng Ai Hospital of TCM, Kunming, ChinaDepartment of Gynecology, Sheng Ai Hospital of TCM, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaBackground Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the potential causal relationships involving gut microbiota-mediated plasma metabolites, inflammatory cytokines, and AAA.Methods We utilized data from genome-wide association studies predominantly comprising individuals of European ancestry, encompassing four major gut microbiota signatures, 233 plasma metabolite signatures (N = 136,016), 91 inflammatory cytokine signatures (N = 14,824), and AAA signatures (N = 1,458,875). Mendelian randomization (MR), employed in a two-sample format, was utilized as a tool to investigate the potential causal pathways from gut microbiota to the development of AAA. Additionally, a two-step MR approach was employed to dissect the impact of plasma metabolites and inflammatory cytokines on the relationship between gut microbiota and AAA and to ascertain the mediated fractions.Results Our findings indicate that five phylum or family-identical bacteria, 175 plasma metabolites, and seven inflammatory factors are causally associated with AAA. Among them, five bacterial species from the same phylum or family, identified from different GWAS data, were strongly associated with AAA. Of these, two exhibited negative causality and three exhibited positive causality. We found that the phylum Firmicutes and the families Oscillospiraceae might reduce the risk of AAA, whereas the families Prevotellaceae, Sutterellaceae, and Aminobacteriaceae might increase the risk of AAA. Further screening indicated that phylum Firmicutes id.1672 (GCST90017114) may confer a protective effect against AAA by reducing triglyceride levels in medium/small high-density lipoprotein (HDL).Conclusion MR analysis has delineated a causal pathway from gut microbiota, through plasma circulating metabolites and inflammatory cytokines, to the pathogenesis of AAA. The role of intestinal flora and certain biomarkers may provide a reference for the diagnosis of AAA, and contribute to the prevention, diagnosis, and treatment of AAA disease.https://www.tandfonline.com/doi/10.1080/10641963.2024.2390419Abdominal aortic aeurysmgut microbiotaplasma metabolitesinflammatory cytokinesMendelian randomizationmediation analyses |
| spellingShingle | Chaozhong Li Zhengqing Liu Siqian Yang Wanrong Li Bo Liang Haoyu Chen Yujia Ye Fang Wang Xiaoqing Liu Yongliang Jiang Haiying Wu Yunzhu Peng Zhaohui Meng Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study Clinical and Experimental Hypertension Abdominal aortic aeurysm gut microbiota plasma metabolites inflammatory cytokines Mendelian randomization mediation analyses |
| title | Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study |
| title_full | Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study |
| title_fullStr | Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study |
| title_full_unstemmed | Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study |
| title_short | Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study |
| title_sort | causal relationship between gut microbiota plasma metabolites inflammatory cytokines and abdominal aortic aneurysm a mendelian randomization study |
| topic | Abdominal aortic aeurysm gut microbiota plasma metabolites inflammatory cytokines Mendelian randomization mediation analyses |
| url | https://www.tandfonline.com/doi/10.1080/10641963.2024.2390419 |
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