PDF(Pubmed)
Abstract：
UNASSIGNED: Recent 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.
UNASSIGNED: Summary 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.
UNASSIGNED: MR 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.
UNASSIGNED: This 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.
UNASSIGNED: Summary 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.
UNASSIGNED: MR 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.
UNASSIGNED: This 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.
摘要：
■最近的研究将肠道菌群和血清代谢物浓度的变化与脑出血（ICH）联系起来。然而,潜在的因果关系尚不清楚.因此,本研究旨在估计肠道微生物群之间遗传预测因果关系的影响，血清代谢物，和ICH。
■来自肠道微生物群的全基因组关联研究（GWAS）的汇总数据，血清代谢物，和ICH分别获得。肠道微生物群GWAS（N=18,340）来自MiBioGen研究，来自TwinsUK和KORA研究的血清代谢物GWAS（N=7,824），和来自FinnGenR9的ICH的GWAS汇总级别数据(ICH，3749例；339,914例控制）。进行了双样本孟德尔随机化（MR）研究，以探索肠道微生物群之间的因果关系，血清代谢物，和ICH。随机效应逆方差加权(IVW)MR分析作为主要结果，以及一系列敏感性分析，以评估结果的稳健性。此外,进行了反向MR以评估反向因果关系的可能性.为了验证相关发现，我们进一步从英国生物库选择数据进行分析.
■MR分析结果揭示了17个肠道微生物分类群之间的名义关联（p<0.05），31血清代谢物，和ICH。在肠道微生物群中，木聚糖真杆菌属水平较高(比值比(OR):1.327,95%置信区间(CI):1.154~1.526;Bonferroni校正p=7.28×10-5),在Bonferroni校正检验后,保留了与ICH风险较高的强因果关系.同时,塞内加尔属（OR：0.843，95％CI：0.778-0.915；Bonferroni校正p=4.10×10-5）与较低的ICH风险相关。此外，Bonferroni校正后,在最初的31种血清代谢物中，仅保留了两种血清代谢物。血清代谢产物之一,异戊酸（OR：7.130，95％CI：2.648-19.199；Bonferroni校正p=1.01×10-4）显示出非常强的因果关系，具有较高的ICH风险，而其他代谢产物未确定,排除在进一步分析之外.各种敏感性分析产生了类似的结果，没有观察到异质性或方向性多效性。
■这项双样本MR研究揭示了肠道微生物群和血清代谢物对ICH风险的显着影响。鉴定了参与ICH开发的特定细菌类群和代谢物。未来需要进一步研究，以更深入地研究这些发现背后的机制。
■来自肠道微生物群的全基因组关联研究（GWAS）的汇总数据，血清代谢物，和ICH分别获得。肠道微生物群GWAS（N=18,340）来自MiBioGen研究，来自TwinsUK和KORA研究的血清代谢物GWAS（N=7,824），和来自FinnGenR9的ICH的GWAS汇总级别数据(ICH，3749例；339,914例控制）。进行了双样本孟德尔随机化（MR）研究，以探索肠道微生物群之间的因果关系，血清代谢物，和ICH。随机效应逆方差加权(IVW)MR分析作为主要结果，以及一系列敏感性分析，以评估结果的稳健性。此外,进行了反向MR以评估反向因果关系的可能性.为了验证相关发现，我们进一步从英国生物库选择数据进行分析.
■MR分析结果揭示了17个肠道微生物分类群之间的名义关联（p<0.05），31血清代谢物，和ICH。在肠道微生物群中，木聚糖真杆菌属水平较高(比值比(OR):1.327,95%置信区间(CI):1.154~1.526;Bonferroni校正p=7.28×10-5),在Bonferroni校正检验后,保留了与ICH风险较高的强因果关系.同时,塞内加尔属（OR：0.843，95％CI：0.778-0.915；Bonferroni校正p=4.10×10-5）与较低的ICH风险相关。此外，Bonferroni校正后,在最初的31种血清代谢物中，仅保留了两种血清代谢物。血清代谢产物之一,异戊酸（OR：7.130，95％CI：2.648-19.199；Bonferroni校正p=1.01×10-4）显示出非常强的因果关系，具有较高的ICH风险，而其他代谢产物未确定,排除在进一步分析之外.各种敏感性分析产生了类似的结果，没有观察到异质性或方向性多效性。
■这项双样本MR研究揭示了肠道微生物群和血清代谢物对ICH风险的显着影响。鉴定了参与ICH开发的特定细菌类群和代谢物。未来需要进一步研究，以更深入地研究这些发现背后的机制。
