肠道菌群与骨质疏松症的遗传关系:来自英国数据库211个肠道微生物群分析  

Genetic causal relationship between gut microbiota and osteoporosis:analysis of 211 gut microbiota from the UK database

作　　者：方志杰 马抢平 董万涛 吴俊媛 陆韵霖 Fang Zhijie;Ma Qiangping;Dong Wantao;Wu Junyuan;Lu Yunlin(Clinical School of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China;Department of Sports Medicine,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China)

机构地区：[1]甘肃中医药大学中医临床学院,甘肃省兰州市730000 [2]甘肃中医药大学附属医院运动医学科,甘肃省兰州市730000

出　　处：《中国组织工程研究》2025年第18期3941-3947,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81960878),项目负责人:董万涛;甘肃省科技计划项目-重点研发计划(21YF5FA017),项目负责人:董万涛;兰州市城关区科技人才创新创业项目(2023-rc-7),项目负责人:董万涛;兰州市科技计划项目(2023-2-83),项目负责人:董万涛。

摘　　要：背景:骨质疏松症被定义为一种慢性代谢性骨病,大量的证据表明肠道菌群与骨质疏松症有关。然而,肠道菌群对骨质疏松症的因果关系尚不清楚。目的:采用双样本孟德尔随机化方法来评估肠道菌群与骨质疏松症之间的潜在因果关系。方法:使用MiBioGen联盟肠道菌群的全基因组关联分析汇总统计数据和英国生物样本数据库中骨质疏松症的全基因组关联分析数据。采用逆方差加权法(Inverse variance weighting,IVW)、MR-Egger回归法、加权中位数法、加权模型法和简单模型法来研究肠道菌群与骨质疏松症之间的因果关系。敏感性分析用于检验孟德尔随机化分析结果是否可靠。结果与结论:逆方差加权法结果表明,肠道菌群与骨质疏松症之间存在因果关系。克里斯滕森菌科R7属(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028)、粪球菌3属(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)和毛螺菌属(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003),可能是骨质疏松的保护性因素,而霍氏菌属(MREgger:β=0.006;IVW:β=0.002,P=0.033)和氧化真杆菌属(MREgger:β=0.001;IVW:β=0.003,P=0.046),可能为骨质疏松症潜在危险性因素。数据分析结果显示,氧化真杆菌属和霍氏菌属可增加骨质疏松风险,克里斯滕森菌科R7属、粪球菌3属和毛螺菌属可降低骨质疏松风险。此结论是否也适用于非欧洲人群,未来需要不同群体的大样本临床试验来验证。BACKGROUND:Osteoporosis is defined as a chronic metabolic bone disease,and a large amount of evidence has shown that gut microbiota is involved in osteoporosis.However,the causal relationship between gut microbiota and osteoporosis is yet unclear.OBJECTIVE:To evaluate the potential causal relationship between gut microbiota and osteoporosis using the two-sample Mendelian randomization.METHODS:Pooled statistics from the MiBioGen Consortium’s Genome-Wide Association Analysis(GWAS)of gut microbiota and GWAS data from the UK Biometric Sample database for osteoporosis were used.Inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted model and simple model were used to study the causal relationship between gut microbiota and osteoporosis.Sensitivity analysis was used to test whether the results of Mendelian randomization are reliable.RESULTS AND CONCLUSION:The inverse variance weighted method showed that there was a causal relationship between gut microbiota and osteoporosis.Among them,the R7 genus of Christensenaceae(MR Egger:β=-0.007;IVW:β=-0.004,P=0.028),Coprococus 3(MR Egger:β=-0.008;IVW:β=-0.003,P=0.046)and Trichospirillum(MR Egger:β=-0.009;IVW:β=-0.004,P=0.003)may be protective factors for osteoporosis,while Hotella(MR Egger:β=0.006;IVW:β=0.002,P=0.033)and Eubacterium oxyoxide(MR Egger:β=0.001;IVW:β=0.003,P=0.046)may be potential risk factors for osteoporosis.Eubacterium oxyoxide and Hotella can increase the risk of osteoporosis,while R7 of Christensenaceae,Coprococcus 3 and Spirillum can reduce the risk of osteoporosis.Whether this conclusion also applies to non-European populations will need to be verified in the future by large clinical trials in different groups.

关 键 词：孟德尔随机化 骨质疏松症 肠道菌群 单核苷酸多态性 因果关系 全基因组关联分析 逆方差加权法 敏感性分析 

分 类 号：R452[医药卫生—治疗学] R318[医药卫生—临床医学] R580