| 免疫细胞介导的肠道菌群与重症肌无力的因果关系 |
| 投稿时间：2025-02-15 修订日期：2025-03-25 点此下载全文 |
| 引用本文：翟阳,庞兴旺,庞延,王瀚,莫智珍,肖裕翰,黎芳,池腾飞,黄桂课.免疫细胞介导的肠道菌群与重症肌无力的因果关系[J].医学研究杂志,2025,54(8):74-79 |
| DOI：
10.11969/j.issn.1673-548X.2025.08.013 |
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| 基金项目:中国博士后科学基金资助项目(2024MD753922)；广西自然科学基金资助项目(2024GXNSFAA010252,2022GXNSFBA035576)；2024年广西青年岐黄学者培养项目(GXQH202419)；广西中医药适宜技术开发与推广项目(GZSY22-73)；广西中医药适宜技术开发与推广项目(GZSY2025086) |
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| 中文摘要:目的 利用双样本孟德尔随机化(Mendelian randomization,MR)分析探讨免疫细胞介导的肠道菌群与重症肌无力(myasthenia gravis,MG)之间的因果关系。方法 借助已发表的分别共涵盖412种肠道菌表型、包含731个免疫细胞表型的全基因组关联研究(genome-wide association study, GWAS)作为暴露因素。从GWAS数据库获取MG的GWAS数据,其中病例组样本量为1278例,对照组样本量为33652例,包含22357218个单核苷酸多态性(single nucleotide polymorphism, SNP)。研究对象均为欧洲人群。首先,采取双样本MR分析方法分别验证肠道菌群与MG、免疫细胞与MG、肠道菌群与免疫细胞之间的因果关系。反向MR验证正向关系。同时进行敏感度分析,包含异质性检验、水平多效性检验、留一法敏感度分析等一系列验证分析。最后,通过两步MR分析法确定免疫细胞在肠道菌群与MG的因果关系中的中介效应。结果 通过逆方差加权法(inverse-variance weighted,IVW)分析免疫细胞介导的肠道菌群与MG的因果关系,结果显示,Barnesiella(OR=1.835,95% CI:1.388~2.426)、Barnesiella_intestinihominis(OR=1.961,95%CI:1.473~2.612)、两形真杆菌种(Eubacterium_biforme)(OR=1.429,95% CI:1.155~1.766)、Bacteroides_clarus(OR=1.220,95% CI:1.017~1.464)、未分类的罗斯菌种(Roseburia_unclassified)(OR=1.260,95% CI:1.053~1.509)与MG发生呈正相关(P＜0.05)；副溶血链球菌种(Streptococcus_parasanguinis)(OR=0.715,95% CI:0.528~0.967)、肠罗斯菌种(Roseburia_intestinalis)(OR=0.712,95% CI:0.517~0.982)与MG发生呈负相关(P＜0.05)；通过系数乘积法得出CD8dim %leukocyte在肠罗斯菌种抑制MG发生、发展过程中的介导作用占总效应的9.25%。结论 肠罗斯菌种通过CD8dim %leukocyte作为中介因子抑制MG的发生、发展。这可能为未来MG的预防、治疗和康复提供新参考和新依据。 |
| 中文关键词:肠道菌 免疫细胞 重症肌无力 孟德尔随机化 中介分析 |
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| Causal Relationship Between Immune Cell-mediated Intestinal Flora and Myasthenia Gravis. |
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| Abstract:Objective To explore the causal relationship between immune cell-mediated intestinal flora and myasthenia gravis (MG) by two-sample Mendelian randomization (MR) analysis. Methods The published Genome-Wide Association Study (GWAS) covering a total of 412 intestinal flora phenotypes and 731 immune cell phenotypes were used as exposure factors. The GWAS data of MG were obtained from the IEU Open GWAS project database. The sample size of the case group was 1278 cases, and the sample size of the control group was 33652 cases, containing 22357218 SNP. The subjects were all Europeans. Firstly, a two-sample MR analysis method was used to verify the causal relationship between intestinal flora and MG, immune cells and MG, intestinal flora and immune cells. Reverse MR verifies the positive relationship. At the same time, sensitivity analysis was carried out, including heterogeneity test, level multi-effect test, leave-one-out sensitivity analysis and a series of verification analysis. Finally, the mediating effect of immune cells in the causal relationship between intestinal flora and MG was determined by two-step MR analysis. Results The causal relationship between immune cell-mediated intestinal flora and MG was analyzed by inverse-variance weighted (IVW) method. The results showed that:Barnesiella (OR=1.835,95% CI:1.388-2.426), Barnesiella_intestinihominis (OR=1.961,95% CI:1.473-2.612), Eubacterium_biforme (OR=1.429,95% CI:1.155-1.766), Bacteroides_clarus (OR=1.220,95% CI:1.017-1.464), Roseburia_unclassified (OR=1.260,95% CI:1.053-1.509) were positively correlated with MG (P<0.05). Streptococcus_parasanguinis (OR=0.715,95% CI:0.528-0.967) and Roseburia_intestinalis (OR=0.712,95% CI:0.517-0.982) were negatively correlated with MG (P<0.05). The coefficient product method showed that the mediating effect of CD8dim % leukocyte in the inhibition of MG development by Roseburia _intestinalis accounted for 9.25% of the total effect. Conclusion Roseburia_intestinalis inhibits the occurrence and development of MG through CD8dim % leukocyte as an intermediary factor. This may provide new reference and basis for the prevention, treatment and rehabilitation of MG in the future. |
| keywords:Gut microbiota Immune cells Myasthenia gravis Mendelian randomization Mediation analysis |
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