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| 孟德尔随机化评估肠道菌群与骨质疏松症之间的因果关系 |
| A Mendelian randomization study to assess the causal relationship between gut microbiota and osteoporosis |
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| DOI：10.3969/j.issn.1006-7108.2025.05.011 |
| 中文关键词: 骨质疏松症 肠道菌群 孟德尔随机化 |
| 英文关键词:osteoporosis gut microbiota Mendelian randomization |
| 基金项目:国家自然科学基金青年项目（81600698）；广东医科大学学科建设类“临床+基础”专项项目（4SG23281G）；广东医科大学博士启动基金（BJ201802） |
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| 中文摘要: |
| 目的 越来越多的证据表明，肠道菌群与骨质疏松症的发生密切相关，但是否存在因果关系尚不明确。本文旨在采用孟德尔随机化（Mendelian randomization，MR）的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 从18 340名参与者的全基因组关联研究（GWAS）汇总数据中确定了肠道菌群的遗传工具变量。骨质疏松症数据也来自GWAS汇总数据，包括7 547例病例和455 386例对照。采用逆方差加权法（IVW）方法进行筛选，进一步采用加权中位数法（WM）、MR- egger回归和敏感性检验（异质性检验、离群值检验、MR-Egger intercept和留一法分析）提高结果的可靠性。结果 经FDR矫正后最终确定了5种肠道菌群与骨质疏松症存在潜在的因果关系，草酸杆菌科相关性优势比(OR)=0.998 3，95 %置信区间（CI）：0.996 8~0.999 7，PFDR=0.034；粪球菌属3 OR=0.996 3，95 % CI：0.993 0~0.999 7，PFDR=0.031；毛螺菌属NK4A136 OR=0.996 2，95 % CI：0.993 9~0.998 5，PFDR=0.006；氧化还原真杆菌属OR=1.002 2，95 % CI：1.000 3~1.004 1，PFDR=0.031；瘤胃球菌属UCG014 OR=1.004 1，95 % CI：1.001 5~1.006 7，PFDR=0.009。其中草酸杆菌科、粪球菌属3和毛螺菌属NK4A136与骨质疏松症的发生呈负相关，氧化还原真杆菌属和瘤胃球菌属UCG014与骨质疏松症的发生呈正相关。结论 肠道菌群与骨质疏松症风险之间存在因果关系。 |
| 英文摘要: |
| Objective There is growing evidence showing that gut microbiota is strongly associated with the development of osteoporosis. However, whether a causal relationship exists is unclear. In this study, Mendelian randomization (MR) was used to assess the potential causal relationship between gut microbiota and osteoporosis. Methods Genetic instrumental variables for gut microbiota were identified from genome-wide association study (GWAS) pooled data from 18340 participants. Osteoporosis data were also derived from GWAS pooled data, including 7547 cases and 455386 controls. Inverse variance weighting (IVW) method was used for screening and further weighted median (WM). MR- Egger regression and sensitivity tests (heterogeneity test, outlier test, MR-Egger intercept and leave-one-out analysis) were used to improve the reliability of the results. Results After FDR correction, five gut microbiota with potential causal relationship with osteoporosis were identified. The correlation dominance ratio (OR) of Oxalobacteraceae family was 0.9983 (95% CI: 0.9968-0.9997, PFDR=0.034). OR of Coprococcus 3 genus was 0.9963 (95% CI: 0.9930-0.9997, PFDR=0.031). OR of Lachnospiraceae NK4A136 group genus was 0.9962 (95% CI: 0.9939-0.9985, PFDR=0.006). OR of Eubacterium oxidoreducens group genus was 1.0022 (95% CI: 1.0003-1.0041, PFDR=0.031). OR of Ruminococcaceae UCG014 genus was 1.0041 (95% CI: 1.0015-1.0067, PFDR=0.009). The family Oxalobacteraceae, the genus Coprococcus 3, and the genus Lachnospiraceae NK4A136 group were negatively associated with the development of osteoporosis. The genus Eubacterium oxidoreducens group and Ruminococcaceae UCG014 were positively associated with the development of osteoporosis. Conclusion A potential causal relationship exists between gut flora and osteoporosis risk. |
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