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目的 运用孟德尔随机化(Mendelian randomization, MR)探讨肠道菌群与骨关节炎(Osteoarthritis, OA)之间的因果关系并鉴定特定菌群分类。方法 基于MiBioGen联盟发布的肠道菌群全基因组关联研究(Genome-wide association study, GWAS)数据，筛选相关的遗传变异位点作为工具变量(Instrumental variables, IVs)。使用两样本双向MR分析，设定全基因组显著性阈值为1.0×10-5,主要采用逆方差加权(Inverse variance weighted, IVW)法，通过效应指标优势比(Odds ratio,OR)及95%置信区间(Confidence interval,CI)评估结果，运用敏感性分析检验结果的异质性及水平多效性，确保MR研究结果稳定可靠。结果 IVW法发现4种肠道菌群与OA显著相关，脱硫弧菌属(Desulfovibrio)[OR=0.851,95%CI(0.737～0.982),P=0.028]、消化球菌属(Peptococcus)[OR=0.888,95%CI(0.808～0.975),P=0.013]与OA呈负相关，为OA的保护因素；厌氧杆菌属(Anaerostipes)[OR=1.228,95%CI(1.025～1.471),P=0.026]、瘤胃梭菌属9(Ruminiclostridium 9)[OR=1.210,95%CI(1.031～1.419),P=0.019]与OA呈正相关，为OA的风险因素。菌群性状的敏感度分析未发现明显的多效性和异质性。结论 本研究在数据库基因预测水平上聚焦肠道菌群与OA之间的潜在因果关系，鉴定出4种与OA存在显著联系的特定肠道菌群作为预防OA的生物学标志物，为肠道菌群在OA预防及治疗中的应用提供了科学依据，也为未来基于肠道菌群干预策略的开发提供了重要启示。
Abstract：Objective Mendelian randomization(MR) was applied to investigate the causal relationship between gut microbiota and osteoarthritis(OA) and to identify the specific microbiota classification. Methods Based on the data of the genome-wide association study(GWAS) on gut microbiota published by MiBioGen Alliance and relevant genetic variation loci were screened as instrumental variables(IVs). Using two-sample and two-way MR analysis, the genome-wide significance threshold was set as 1.0×10-5, and Inverse variance weighted(IVW) method was adopted. The results were evaluated by the odds ratio(OR) and 95% confidence interval(CI), and the heterogeneity and horizontal pleiotropy of the results were tested by sensitivity analysis to ensure the stability and reliability of the MR study results. Results IVW method shows that 4 types of intestinal flora are significantly correlated with OA, Desulfovibrio [OR=0.851, 95%CI(0.737-0.982), P=0.028], Peptococcus [OR=0.888, 95%CI(0.808-0.975), P=0.013] was negatively correlated with OA, and was a protective factor for OA. Anaerostipes [OR=1.228, 95%CI(1.025-1.471), P=0.026], Ruminiclostridium 9 [OR=1.210, 95%CI(1.031-1.419), P=0.019] was positively correlated with OA and was a risk factor for OA. Sensitivity analysis of bacterial community traits did not show significant pleiotropy and heterogeneity. Conclusion This study focused on the potential causal relationship between gut microbiota and OA at the level of database gene prediction, and identified 4 specific gut microbiota with significant association with OA as biological indicators for the prevention of OA, providing a scientific basis for the application of gut microbiota in the prevention and treatment of OA, and also providing important inspiration for the development of future intervention strategies based on gut microbiota.
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基本信息:
中图分类号:R684.3
引用信息:
[1]李文娟,张远,李思琦,等.全基因组关联研究数据库探讨肠道菌群与骨关节炎之间的因果关系[J].新疆医科大学学报,2025,48(04):456-463.
基金信息:
“天山英才”医药卫生高层次人才培养计划项目(TSYC202301B091); 新疆维吾尔自治区自然科学基金项目(2022D01C475)
2025-04-15
2025-04-15