摘要
目的本研究采用了两样本孟德尔随机化(TSMR)方法,以探讨肠道菌群与胶质母细胞瘤(GBM)之间可能存在的因果关系。方法从211个与肠道微生物群相关的大规模全基因组关联研究(GWAS)中筛选与GBM发病相关的单核苷酸多态性(SNP),以作为工具变量。研究中主要采用逆方差加权(IVW)方法来评估因果效应,同时进行了异质性检验、多效性检验以及敏感性分析,以确保结果的可靠性。此外,研究还针对水平多效性异常值的SNP进行了剔除处理,从而增强了研究结论的有效性。结果通过IVW分析发现9种肠道菌群与GBM之间存在潜在关联,其中短优杆菌属和消化链球菌属增加GBM发生风险,而瘤胃球菌属、厌氧菌属、普雷沃菌属、普拉梭菌、考拉杆菌属、毛螺菌属、链球菌可降低GBM发生风险,9种微生物属在通过异质和水平多效性方面保持稳定。同时通过严格的BH矫正后,发现瘤胃球菌属对GBM起保护作用(OR_(IVW)=0.036,95%CI:0.007~0.191,P_(BH)=0.003)。结论瘤胃球菌属、普氏菌属等7种菌群在GBM发生发展中存在潜在保护作用,短优杆菌属和消化链球菌属是GBM发生的潜在危险因素。调节肠道微生物群对预防和治疗GBM具有良好的临床意义。
Objective This study employed the two-sample mendelian randomization(TSMR)method to investigate the potential causal relationship between intestinal flora and glioblastoma(GBM).Methods The research utilized Mendelian randomization(MR)approach to identify single nucleotide polymorphisms(SNPs)associated with the onset of brain glioblastoma from 211 large-scale genome-wide association studies(GWAS)related to intestinal microbiota.SNPs were used as instrumental variables.The inverse variance weighting(IVW)method was primarily applied to assess the causal effect,while heterogeneity testing,pleiotropy assessment,and sensitivity analysis were performed to ensure the reliability of the findings.Furthermore,the study excluded SNPs with horizontal pleiotropy outliers,thereby enhancing the validity of the conclusions.Results Mendelian randomization analysis revealed potential associations between nine gut microbiota species and glioblastoma(GBM).Specifically,an increased risk of GBM was observed in the presence of Eubacterium brachygroup and Peptostreptococcaceae,while Ruminococcaceae,Prevotella,Faecalibacterium,Phascolarctobacterium,Anaerostipes,Lachnospiraceae,and Streptococcus were associated with a decreased risk of GBM.These nine microbial species demonstrated stability in terms of heterogeneity and horizontal pleiotropy.Furthermore,after rigorous BH correction,Ruminococcaceae was found to exhibit a protective effect against GBM(OR_(IVW)=0.036,95%CI:0.007-0.191,P_(BH)=0.003).Conclusion This study demonstrates that the taxa Ruminococcaceae and Prevotella exert a protective role against the occurrence and development of glioblastoma(GBM),whereas the genera Eubacteriumbrachygroup and Peptostreptococcaceae are potential risk factors for GBM.Modulating the gut microbiota presents promising clinical implications for the prevention and treatment of GBM.
作者
何鹏
华靖华
巩守平
HE Peng;HUA Jinghua;GONG Shouping(Department of Neurosurgery,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710000,China)
出处
《西部医学》
2025年第9期1305-1310,共6页
Medical Journal of West China
基金
陕西省重点研发计划项目(2022ZDLSF04-01)。
