免疫介导肠道微生物群和多发性骨髓瘤之间的因果关系：孟德尔随机化研究-现代医学

免疫介导肠道微生物群和多发性骨髓瘤之间的因果关系：孟德尔随机化研究

单位：1. 山西医科大学附属运城市中心医院血液内科, 山西运城 044000;
2. 山西医科大学附属运城市中心医院肾脏内科, 山西运城 044000;
3. 山西医科大学附属运城市中心医院健康促进办公室, 山西运城 044000

分类号：R733.3

出版年·卷·期（页码）：2025·53·第七期（1038-1049）

摘要：

目的：多发性骨髓瘤(multiple myeloma，MM)是较常见的恶性血液系统疾病，肠道微生物和免疫可能影响了MM的发病与进展，但是它们之间的因果关系尚不清楚。本研究拟利用孟德尔随机化(Mendelian randomization，MR)探索肠道微生物群(gut microbiota，GM)、免疫细胞表型与MM之间的因果关系，并确立免疫细胞的中介作用。方法：通过全基因组关联研究数据，以GM作为暴露，免疫细胞表型作为中介，MM作为结局，基于两步MR方法探索731种免疫细胞表型在其中的中介作用。首先利用逆方差加权法及多种方法评估GM与MM、免疫细胞表型和MM的因果关系，在确定与MM具有显著因果关系的GM和免疫细胞后，进一步探索当前 GM和免疫细胞表型的因果关系。结果：有9种肠道微生物(1纲、1目、2科、2属和3种)和MM存在因果关系，同时有42种免疫细胞表型和MM存在因果关联。在这些具有因果关系的GM和免疫细胞中，一共存在7对因果关系。经过中介分析后，IgD⁺ CD24⁺ 细胞表面表达IgD计数介导了Veillonellaceae和MM的风险(中介效应=5.91%)，中央记忆性CD4⁺ T细胞表面表达CD3计数(中介效应=7.28%)和分泌型调节性T细胞表面表达CD3计数(中介效应=6.70%)均介导了Ruminococcus1对MM的风险。所有的敏感性分析结果都进一步增强了结果的稳健性。结论：GM、免疫细胞表型与MM之间均存在显著的因果关系。通过GM来进行免疫调节从而对MM进行预防、监测和治疗是一种前景广阔的方法。

Objective:To explore the causal relationship between gut microbiota(GM), immune cell phenotypes, and multiple myeloma(MM) using Mendelian randomization(MR), and to establish the mediating role of immune cells. Method： Using data from genome-wide association studies, the mediating role of 731 immune cell phenotypes were explored based on two-step MR methods, with GM as exposure, immune cell phenotype as the mediator, and MM as the outcome. The causal associations of GM with MM, immune cell phenotype and MM were first assessed using inverse variance weighted method and multiple methods. After identifying GM and immune cells with significant causal relationships with MM, the causal relationships between current GM and immune cell phenotypes were further explored. Results:The results suggested a causal relationship between 9 types of gut microbiota(1 class, 1 order, 2 families, 2 genera, and 3 species) and MM. Additionally, 42 immune cell phenotypes were causally associated with MM. Among these, there were 7 pairs with causal relationships between GM and immune cells. Mediator analysis indicated that IgD on IgD⁺ CD24⁺ mediated the risk of Veillonellaceae for MM(mediating effect=5.91%), CD3 on CM CD4⁺(mediating effect=7.28%), and CD3 on secreting Treg(mediating effect=6.70%) both mediated the risk of Ruminococcus1 for MM. Sensitivity analyses further strengthened the robustness of the results.Conclusion:There is a significant causal relationship between GM, immune cell phenotypes, and MM. Modulating the immune system via GM to prevent, monitor, and treat MM is a promising approach.

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