首页|期刊导航|中华骨质疏松和骨矿盐疾病杂志|肠道菌群、血浆蛋白与2型糖尿病性骨质疏松症:一项孟德尔随机化研究

肠道菌群、血浆蛋白与2型糖尿病性骨质疏松症:一项孟德尔随机化研究OA

Gut microbiota,plasma proteins,and type 2 diabetic osteoporosis:A Mendelian randomization Study

中文摘要英文摘要

目的 探讨肠道菌群与 2 型糖尿病性骨质疏松症(type 2 diabetic osteoporosis,T2DOP)的因果关系,并评估血浆蛋白在二者关系中的潜在中介作用.方法 采用两样本孟德尔随机化(two-sample Mendelian randomization,MR)设计,基于来自肠道菌群(n=8 208)、血浆蛋白(n=4 719)及 2 型糖尿病性骨质疏松症(1 301 例病例与 38 317 例对照)的汇总水平数据进行分析.以逆方差加权法(inverse variance weighting,IVW)为主要统计方法,以估计因果效应,同时进行多种敏感性分析以验证结果的稳健性与因果推断方向的可靠性.此外,通过两步孟德尔随机化分析(two-step MR)进一步评估血浆蛋白在肠道菌群与T2DOP 发生之间的潜在中介作用.结果 在遗传预测的肠道微生物群组成与 T2DOP 之间,发现了 2 种正向因果关联和 3 种负向因果关联.在血浆蛋白与 T2DOP 之间,观察到 21 种正向因果关联和 23 种负向因果关联.没有证据表明血浆蛋白在肠道微生物群与 T2DOP 之间的关系中起中介作用.结论 肠道菌群及血浆蛋白均与2 型糖尿病性骨质疏松症存在因果关联,但血浆蛋白似乎并非肠道菌群影响 T2DOP 的中介因素.

Objective To investigate the causal relationship between gut microbiota and type 2 diabetic osteopo-rosis(T2DOP)and to evaluate the potential mediating role of plasma proteins in this association.Methods This study employed a two-sample Mendelian randomization(MR)design using summary-level data from genome-wide association studies of gut microbiota(n=8 208),plasma proteins(n=4 719),and T2DOP(1 301 cases and 38 317 controls).The inverse variance weighted(IVW)method was applied as the primary approach to estimate causal effects,comple-mented by multiple sensitivity analyses to assess the robustness and reliability of the findings and the direction of causality.Furthermore,a two-step MR analysis was conducted to evaluate the potential mediating role of plasma proteins in the rela-tionship between gut microbiota and T2DOP.Results Genetically predicted gut microbiota composition showed two posi-tive and three negative causal associations with T2DOP.In addition,21 positive and 23 negative causal associations were identified between plasma proteins and T2DOP.However,no evidence supported a mediating role of plasma proteins in the association between gut microbiota and T2DOP.Conclusion Our findings suggest that both gut microbiota and plasma proteins are causally associated with T2DOP.Nevertheless,plasma proteins do not appear to mediate the effect of gut mi-crobiota on the development of T2DOP.

陈宝瑞;武嘉鑫;雷署丰;柏林

215004 江苏苏州,苏州大学附属第二医院风湿免疫科215123 江苏苏州,苏州大学公共卫生学院流行病学与遗传流行病学中心215123 江苏苏州,苏州大学公共卫生学院流行病学与遗传流行病学中心215004 江苏苏州,苏州大学附属第二医院风湿免疫科

医药卫生

肠道菌群2型糖尿病性骨质疏松症血浆蛋白孟德尔随机化

gut microbiotatype 2 diabetic osteoporosisplasma proteinsMendelian randomization

《中华骨质疏松和骨矿盐疾病杂志》 2026 (2)

217-234,18

国家自然科学基金面上项目(82271612)苏州市姑苏卫生健康领军人才计划领军人才科研项目(GSWS2022047)教育部老年医学与免疫学重点实验室开放课题(KJS2402)苏州大学临床医学高峰培育计划"临床医师科学家"(ML12300423)苏州大学第二附属医院学科建设助推计划"医学+X"创新团队项目(XKTJ-TD202407)

10.3969/j.issn.1674-2591.2026.02.008

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