中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (18): 3941-3947.doi: 10.12307/2025.679

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    下一篇

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

方志杰1,马抢平1,董万涛2,吴俊媛1,陆韵霖1   

  1. 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
  • 收稿日期:2024-07-06 接受日期:2024-08-26 出版日期:2025-06-28 发布日期:2024-11-29
  • 通讯作者: 董万涛,主任医师,博士生导师,甘肃中医药大学附属医院运动医学科,甘肃省兰州市 730000
  • 作者简介:方志杰,男,1998年生,甘肃省武威市人,汉族,甘肃中医药大学在读硕士,主要从事中医药防治骨伤疾病研究。
  • 基金资助:
    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

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

Fang Zhijie1, Ma Qiangping1, Dong Wantao2, Wu Junyuan1, Lu Yunlin1     

  1. 1Clinical School of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China; 2Department of Sports Medicine, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
  • Received:2024-07-06 Accepted:2024-08-26 Online:2025-06-28 Published:2024-11-29
  • Contact: Dong Wantao, Chief physician, Doctoral supervisor, Department of Sports Medicine, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
  • About author:Fang Zhijie, Master candidate, Clinical School of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
  • Supported by:
     National Natural Science Foundation of China, No. 81960878 (to DWT); Key Research and Development Plan of Gansu Province, No. 21YF5FA017 (to DWT); Innovation and Entrepreneurship Project of Science and Technology Talents of Chengguan District of Lanzhou City, No. 2023-rc-7 (to DWT); Science and Technology Plan of Lanzhou City, No. 2023-2-83 (to DWT) 

摘要:


文题释义:
肠道菌群:是在人体肠道中生存的数量庞大、种类多样的微生物集合。
孟德尔随机化:是一种流行病学技术,它借助遗传变异作为工具变量,以推断暴露因素与疾病或健康结果之间的因果关联。

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(MR Egger:β=0.006;IVW:β=0.002,P=0.033)和氧化真杆菌属(MR Egger: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。
https://orcid.org/0009-0007-5702-3851(方志杰)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

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

Abstract: 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.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: Mendelian randomization, osteoporosis, gut microbiota, single nucleotide polymorphism, causal relationship, genome-wide association analysis, inverse variance weighting method, sensitivity analysis

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