中国组织工程研究2025，Vol.29Issue(35)：7663-7668,6.DOI:10.12307/2026.536
肠道菌群与类风湿关节炎的因果关系:GWAS数据欧洲群体资料分析
Causal relationship between gut microbiota and rheumatoid arthritis:data analysis in European populations based on GWAS data
摘要
Abstract
BACKGROUND:Studies have shown that gut microbiota may affect the progression of rheumatoid arthritis.However,the causal relationship between the two is unknown.Mendelian randomization analysis of the two using published Genome Wide Association Study(GWAS)data can explore the causal relationship between gut microbiota and rheumatoid arthritis,helping to develop targeted microbial therapies and provide methods and strategies for the prevention and treatment of rheumatoid arthritis. OBJECTIVE:To explore the potential causal relationship between gut microbiota and rheumatoid arthritis using two-sample two-way Mendelian randomization method. METHODS:Gut microbiota GWAS data from the MiBio-Gen consortium and rheumatoid arthritis GWAS data from the IEU Open GWAS database(a large gene-phenotype association database developed at the MRC Integrative Epidemiology Unit(IEU)at the University of Bristol,UK)were used.Inverse variance weighting was used as the main analysis method,and MR-Egger regression method,weighted median method,weighted model and simple model method were used as supplements to study the causal relationship between gut microbiota and rheumatoid arthritis.Heterogeneity was assessed using Cochran's Q test,horizontal pleiotropy was assessed using MR-PRESSO and MR-Egger intercept tests,robustness of results was tested using leave-one method,and reverse Mendelian randomization analysis was used to assess the presence or absence of reverse causality. RESULTS AND CONCLUSION:(1)There was a causal relationship between five kinds of enteric bacteria and rheumatoid arthritis.Ruminococcus gauvreauii group(β=0.262,odds ratio[OR]=1.300,P=0.013)and Butyricimonas(β=0.001,OR=1.001,P=0.014)increased the risk of rheumatoid arthritis,while Anaerostipes(β=-0.225,OR=0.798,P=0.025),Lachnospiraceae-UCG010(β=-0.177,OR=0.838,P=0.026)and Oxalobacter(β=-0.171,OR=0.843,P=0.001)reduced the risk of rheumatoid arthritis.Sensitivity analyses showed no significant heterogeneity or horizontal pleiotropy(all P＞0.05),and leave-one-out testing confirmed the robustness of the results,while the addition of the remaining four methods other than the inverse variance weighting method further validated the reliability and stability of the results.(2)Reverse Mendelian randomization analysis did not find a causal association between rheumatoid arthritis and the five kinds of enteric bacteria identified by Mendelian randomization analysis.These findings indicate that Ruminococcus gauvreauii group and Butyricimonas may be the risk factors of rheumatoid arthritis,while Anaerostipes,Lachnospiraceae-UCG010 and Oxalobacter may be the protective factors of rheumatoid arthritis.Gut microbiota may play an important role in the pathogenesis of rheumatoid arthritis,and provide new biomarkers for the prevention and treatment of rheumatoid arthritis.In addition,for the field of biomedical research in China,we can learn from international experience and gradually establish and improve a multi-center large-scale genetic database,so as to deeply explore the relationship between gut microbiota and disease risk,and promote the development of precision medicine and personalized treatment in China.关键词
肠道菌群/类风湿关节炎/孟德尔随机化/因果关系/逆方差加权法Key words
gut microbiota/rheumatoid arthritis/Mendelian randomization/causality/inverse variance weighting method分类
医药卫生引用本文复制引用
汪涛,王顺谱,闵友江,王敏,李乐,张宸,肖伟平..肠道菌群与类风湿关节炎的因果关系:GWAS数据欧洲群体资料分析[J].中国组织工程研究,2025,29(35):7663-7668,6.基金项目
全国名老中医药专家传承工作室建设项目(赣财社指[2024]39号),项目负责人:肖伟平 National Famous Elderly Chinese Medicine Experts Inheritance Workshop Construction Project,No.[2024]39(XWP) （赣财社指[2024]39号）
