帕金森病与肠道菌群的因果关系

Mendelian randomization-based investigation of the causal relationship between Parkinson's disease and gut microbiota

目的使用孟德尔随机化技术研究肠道菌群与帕金森病(PD)之间的相关性。方法从MiBioGen联盟发表的肠道微生物组全基因组关联研究(GWAS)中获取汇总统计数据,筛选遗传变异点作为工具变量。两样本孟德尔随机化分析主要采用逆方差加权法,根据效应指标优势比(OR)和95%置信区间(CI)评估结果。通过敏感性分析检验异质性、水平多效性及结果稳定性。结果IVW方法中,霍氏肠杆菌[OR=1.2,95%CI(1.00,2.26),P=0.05]、发酵性厌氧梭菌[OR=1.19,95%CI(1.04,1.37),P=0.01]、粪杆菌属[OR=1.20,95%CI(1.00,1.52)P=0.05]、狭义梭菌属1[OR=1.36,95%CI(1.09,1.69),P=0.01]均与PD呈正相关。敏感度分析显示无反向因果关系、多效性和异质性的证据。结论本研究聚焦于肠道微生物群与PD之间的潜在因果联系,筛选并鉴定了多种与PD存在显著联系的特定肠道微生物。这些肠道微生物具有作为预测或诊断PD的生物学指标潜力,可能为开发基于肠道菌群的预防性对策及治疗手段提供新颖的观点。

Objective Study the correlation between gut microbiota and Parkinson's disease(PD)using Mendelian randomization techniques.Methods Summary statistics were obtained from the gut microbiome Genomewide Association Studies(GWAS)published by the MiBioGen consortium,and genetic variants were screened as instrumental variables.Bidirectional Mendelian randomization analyses were primarily performed using the inversevariance weighted method,assessing the results based on the effect estimate Odds Ratio(OR)and the 95%Confidence Interval(CI).Heterogeneity,pleiotropy,and the stability of the results were examined through sensitivity analyses.Results In the IVW method,a positive association with PD was noted for eubacterium hallii group[OR=1.20,95%CI(1.00,2.26),P=0.05],potential candidatus soleaferrea[OR=1.19,95%CI(1.04,1.37),P=0.01],[OR=1.23,95%CI(1.00,1.52),P=0.05],and clostridium sensu stricto 1[OR=1.36,95%CI(1.09,1.69),P=0.01].Sensitivity analyses revealed no evidence of reverse causation,pleiotropy,or heterogeneity.Conclusion This study focused on the potential causal link between the gut microbiota and PD screening and identifying various specific intestinal microbes that have a significant association with PD.These gut microbes hold the potential to serve as biomarkers for predicting or diagnosing PD and may offer novel perspectives for developing preventative strategies and therapeutic approaches based on the gut microbiome.