Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study
BackgroundRecent research linked changes in the gut microbiota and serum metabolite concentrations to intracerebral hemorrhage (ICH). However, the potential causal relationship remained unclear. Therefore, the current study aims to estimate the effects of genetically predicted causality between gut...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1257405/full |
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| author | Tianlong Zhang Gang Liu Yina Cao Jianqiang Zhao Siyi Jiang Ya Zhang Min Li |
| author_facet | Tianlong Zhang Gang Liu Yina Cao Jianqiang Zhao Siyi Jiang Ya Zhang Min Li |
| author_sort | Tianlong Zhang |
| collection | DOAJ |
| description | BackgroundRecent research linked changes in the gut microbiota and serum metabolite concentrations to intracerebral hemorrhage (ICH). However, the potential causal relationship remained unclear. Therefore, the current study aims to estimate the effects of genetically predicted causality between gut microbiota, serum metabolites, and ICH.MethodsSummary data from genome-wide association studies (GWAS) of gut microbiota, serum metabolites, and ICH were obtained separately. Gut microbiota GWAS (N = 18,340) were acquired from the MiBioGen study, serum metabolites GWAS (N = 7,824) from the TwinsUK and KORA studies, and GWAS summary-level data for ICH from the FinnGen R9 (ICH, 3,749 cases; 339,914 controls). A two-sample Mendelian randomization (MR) study was conducted to explore the causal effects between gut microbiota, serum metabolites, and ICH. The random-effects inverse variance-weighted (IVW) MR analyses were performed as the primary results, together with a series of sensitivity analyses to assess the robustness of the results. Besides, a reverse MR was conducted to evaluate the possibility of reverse causation. To validate the relevant findings, we further selected data from the UK Biobank for analysis.ResultsMR analysis results revealed a nominal association (p < 0.05) between 17 gut microbial taxa, 31 serum metabolites, and ICH. Among gut microbiota, the higher level of genus Eubacterium xylanophilum (odds ratio (OR): 1.327, 95% confidence interval (CI):1.154–1.526; Bonferroni-corrected p = 7.28 × 10−5) retained a strong causal relationship with a higher risk of ICH after the Bonferroni corrected test. Concurrently, the genus Senegalimassilia (OR: 0.843, 95% CI: 0.778–0.915; Bonferroni-corrected p = 4.10 × 10−5) was associated with lower ICH risk. Moreover, after Bonferroni correction, only two serum metabolites remained out of the initial 31 serum metabolites. One of the serum metabolites, Isovalerate (OR: 7.130, 95% CI: 2.648–19.199; Bonferroni-corrected p = 1.01 × 10−4) showed a very strong causal relationship with a higher risk of ICH, whereas the other metabolite was unidentified and excluded from further analysis. Various sensitivity analyses yielded similar results, with no heterogeneity or directional pleiotropy observed.ConclusionThis two-sample MR study revealed the significant influence of gut microbiota and serum metabolites on the risk of ICH. The specific bacterial taxa and metabolites engaged in ICH development were identified. Further research is required in the future to delve deeper into the mechanisms behind these findings. |
| first_indexed | 2024-03-08T13:28:34Z |
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| spelling | doaj.art-836f122a5f7d495ead92c501a168f4402024-01-17T12:26:00ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-01-011510.3389/fmicb.2024.12574051257405Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization studyTianlong Zhang0Gang Liu1Yina Cao2Jianqiang Zhao3Siyi Jiang4Ya Zhang5Min Li6Department of Critical Care Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, ChinaDepartment of Infection Control, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, ChinaDepartment of Neurology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, ChinaDepartment of Cardiology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, ChinaDepartment of Critical Care Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, ChinaDepartment of Pharmacy, Yiwu Hospital of Traditional Chinese Medicine, Yiwu, Zhejiang, ChinaDepartment of Critical Care Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, ChinaBackgroundRecent research linked changes in the gut microbiota and serum metabolite concentrations to intracerebral hemorrhage (ICH). However, the potential causal relationship remained unclear. Therefore, the current study aims to estimate the effects of genetically predicted causality between gut microbiota, serum metabolites, and ICH.MethodsSummary data from genome-wide association studies (GWAS) of gut microbiota, serum metabolites, and ICH were obtained separately. Gut microbiota GWAS (N = 18,340) were acquired from the MiBioGen study, serum metabolites GWAS (N = 7,824) from the TwinsUK and KORA studies, and GWAS summary-level data for ICH from the FinnGen R9 (ICH, 3,749 cases; 339,914 controls). A two-sample Mendelian randomization (MR) study was conducted to explore the causal effects between gut microbiota, serum metabolites, and ICH. The random-effects inverse variance-weighted (IVW) MR analyses were performed as the primary results, together with a series of sensitivity analyses to assess the robustness of the results. Besides, a reverse MR was conducted to evaluate the possibility of reverse causation. To validate the relevant findings, we further selected data from the UK Biobank for analysis.ResultsMR analysis results revealed a nominal association (p < 0.05) between 17 gut microbial taxa, 31 serum metabolites, and ICH. Among gut microbiota, the higher level of genus Eubacterium xylanophilum (odds ratio (OR): 1.327, 95% confidence interval (CI):1.154–1.526; Bonferroni-corrected p = 7.28 × 10−5) retained a strong causal relationship with a higher risk of ICH after the Bonferroni corrected test. Concurrently, the genus Senegalimassilia (OR: 0.843, 95% CI: 0.778–0.915; Bonferroni-corrected p = 4.10 × 10−5) was associated with lower ICH risk. Moreover, after Bonferroni correction, only two serum metabolites remained out of the initial 31 serum metabolites. One of the serum metabolites, Isovalerate (OR: 7.130, 95% CI: 2.648–19.199; Bonferroni-corrected p = 1.01 × 10−4) showed a very strong causal relationship with a higher risk of ICH, whereas the other metabolite was unidentified and excluded from further analysis. Various sensitivity analyses yielded similar results, with no heterogeneity or directional pleiotropy observed.ConclusionThis two-sample MR study revealed the significant influence of gut microbiota and serum metabolites on the risk of ICH. The specific bacterial taxa and metabolites engaged in ICH development were identified. Further research is required in the future to delve deeper into the mechanisms behind these findings.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1257405/fullgut microbiotaserum metabolitesintracerebral hemorrhagegenomewide association studiesMendelian randomization |
| spellingShingle | Tianlong Zhang Gang Liu Yina Cao Jianqiang Zhao Siyi Jiang Ya Zhang Min Li Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study Frontiers in Microbiology gut microbiota serum metabolites intracerebral hemorrhage genomewide association studies Mendelian randomization |
| title | Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study |
| title_full | Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study |
| title_fullStr | Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study |
| title_full_unstemmed | Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study |
| title_short | Genetically predicted causality between gut microbiota, blood metabolites, and intracerebral hemorrhage: a bidirectional Mendelian randomization study |
| title_sort | genetically predicted causality between gut microbiota blood metabolites and intracerebral hemorrhage a bidirectional mendelian randomization study |
| topic | gut microbiota serum metabolites intracerebral hemorrhage genomewide association studies Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1257405/full |
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