【摘要】 目的 本研究旨在通过孟德尔随机化(Mendelian randomization, MR)方法探讨肠道微生物群与虚弱之间的因果关系，并评估免疫细胞在这一关系中的中介或遮掩效应。方法 从GWAS Catalog数据库中提取了473种肠道微生物分类群、731种免疫细胞特征以及虚弱的全基因组关联数据。采用两样本MR方法评估肠道微生物与虚弱之间的因果关系。为了识别免疫细胞的中介或遮掩效应，应用两步MR策略，并通过反向MR分析验证肠道微生物→免疫细胞→虚弱的因果中介作用路径方向的单向性。结果 研究发现4种肠道微生物分类群和17种免疫细胞特征与虚弱存在因果关系。中介分析进一步揭示了两条因果中介作用路径：Faecalicoccus属→CD28+CD45RA+CD8br AC→虚弱，Lachnospira rogosae种→CD62L-CD86+myeloid DC%DC→虚弱。免疫细胞特征在这两条路径中均表现为遮掩效应，反向MR分析支持路径的单向性。结论 本研究识别的因果关联和中介效应，为基于肠道微生物群和免疫细胞的虚弱管理策略开发提供了理论依据和研究方向。更多还原

【Abstract】 Objective This study aims to explore the causal relationship between gut microbiota and frailty using Mendelian randomization(MR) methods and assess the potential mediating or masking effects of immune cells in this relationship.Methods Genome-wide association study data for 473 gut microbiota taxa, 731 immune cell characteristics, and frailty were extracted from the GWAS Catalog. A two-sample MR approach was employed to evaluate the causal relationship between gut microbiota and frailty. To identify the mediating or masking effects of immune cells, a two-step MR strategy was applied, and reverse MR analysis was conducted to validate the unidirectional nature of the causal mediation pathway(gut microbiota →immune cells → frailty). Results The study found that 4 gut microbiota taxa and 17 immune cell characteristics had causal associations with frailty. Mediation analysis revealed two causal mediation pathways: phylum Firmicutes A → CD28 +CD45RA + CD8br AC → frailty, and species Lachnospira rogosae → CD62L-CD86 + myeloid DC %DC → frailty. Immune cell characteristics acted as masking effects in both pathways, and reverse MR analysis supported the unidirectional nature of these causal relationships. Conclusion The causal associations and mediation effects identified in this study provide a theoretical basis and direction for the development of frailty management strategies based on gut microbiota and immune cells.更多还原