中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (6): 1296-1304.doi: 10.12307/2025.311

• 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性骨折

赵文生1,李孝林2,彭昌华3,邓  佳1,盛  浩1,陈洪卫3,张朝驹3,何  川1,3   

  1. 1湖北中医药大学,湖北省武汉市  430061;2长江大学,湖北省荆州市  434023;3湖北中医药大学附属荆州市中医医院,湖北省荆州市  434000
  • 收稿日期:2024-02-08 接受日期:2024-03-28 出版日期:2025-02-28 发布日期:2024-06-24
  • 通讯作者: 何川,硕士,湖北中医药大学兼职副教授,硕士生导师,主任医师,湖北中医药大学,湖北省武汉市 430061;湖北中医药大学附属荆州市中医医院,湖北省荆州市 434000 并列通讯作者:李孝林,博士,副教授,长江大学医学部,湖北省荆州市 434023
  • 作者简介:赵文生,1998年生,江西省赣州市人,湖北中医药大学在读硕士研究生,医师,主要从事脊柱外科方面的研究。
  • 基金资助:
    全国名老中医专家传承工作室建设项目(国中医药人教函[2022]75号),项目负责人:张朝驹;湖北省自然科学基金面上项目(2022CFB054),项目负责人:李孝林;湖北省中医药管理局中医药科研面上项目(ZY2023M051),项目负责人:何川;荆州市中医药研究所自主选题项目(ZZXT2023Y07),项目负责人:彭昌华

Gut microbiota and osteoporotic fractures #br#
#br#

Zhao Wensheng1, Li Xiaolin2, Peng Changhua3, Deng Jia1, Sheng Hao1, Chen Hongwei3, Zhang Chaoju3, He Chuan1, 3     

  1. 1Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China; 2Yangtze University, Jingzhou 434023, Hubei Province, China; 3Jingzhou Hospital of Traditional Chinese Medicine Affiliated to Hubei University of Chinese Medicine, Jingzhou 434000, Hubei Province, China
  • Received:2024-02-08 Accepted:2024-03-28 Online:2025-02-28 Published:2024-06-24
  • Contact: He Chuan, Master, Associate professor, Master’s supervisor, Chief physician, Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China; Jingzhou Hospital of Traditional Chinese Medicine Affiliated to Hubei University of Chinese Medicine, Jingzhou 434000, Hubei Province, China Co-corresponding author: Li Xiaolin, MD, Associate professor, Yangtze University, Jingzhou 434023, Hubei Province, China
  • About author:Zhao Wensheng, Master candidate, Physician, Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China
  • Supported by:
    the Construction Project of National Famous Traditional Chinese Medicine Expert Inheritance Workshop, No. [2022]75 (to ZCJ); Hubei Province Natural Science Foundation, No. 2022CFB054 (to LXL); Chinese Medicine Research Project of Hubei Administration of Chinese Medicine, No. ZY2023M051 (to HC); Jingzhou Institute of Traditional Chinese Medicine Independent Topic Project, No. ZZXT2023Y07 (to PCH)

摘要:




文题释义:
孟德尔随机化研究:孟德尔随机化是一种基于遗传变异的因果推断方法,与传统的流行病学研究相比,孟德尔随机化使用遗传变异作为工具变量,有效地避免了混杂因素和反向因果关系的影响,是确定暴露因素与结局变量之间因果关系的可靠手段。
肠道菌群:是存在于人体内的最大微生物菌群,在长期共同进化过程中肠道菌群与人体相互依赖,形成了互利共生的关系,它们不仅可以影响食物的消化吸收,还具有参与人体代谢和调节免疫应答等功能,对人体健康起着至关重要的作用。

背景:骨质疏松性骨折是骨质疏松症最严重的并发症,既往的研究已经证实了肠道菌群对骨骼组织具有调节作用,肠道菌群与骨质疏松性骨折有着重要关系,但是二者之间的因果关系尚不清楚。
目的使用孟德尔随机化(MR)方法探索肠道菌群与骨质疏松性骨折之间的因果关系。
方法:从IEU Open GWAS数据库和芬兰数据库R9中分别获得了肠道菌群和骨质疏松性骨折的GWAS数据集,以肠道菌群作为暴露因素,骨质疏松性骨折作为结局变量,采用随机效应逆方差加权法、MR-Egger回归、加权中位数法、简单模型法以及加权模型法进行孟德尔随机化分析来评估肠道菌群与骨质疏松性骨折之间是否存在因果关系,通过敏感性分析来检验结果的可靠性和稳健性,并进行反向孟德尔随机化分析来进一步验证正向孟德尔随机化分析中确定的因果关系。
结果与结论:①此孟德尔随机化分析结果表明,肠道菌群与骨质疏松性骨折之间存在因果关系。放线菌目(OR=1.562,95%CI:1.027-2.375,P=0.037)、放线菌科(OR=1.561,95%CI:1.027-2.374,P=0.037)、放线菌属(OR=1.544,95%CI:1.130-2.110,P=0.006)、丁酸球菌属(OR=1.781,95%CI:1.194-2.657,P=0.005)、粪球菌属-2(OR=1.550,95%CI:1.068-2.251,P=0.021)、Family XIII UCG-001属(OR=1.473,95%CI:1.001-2.168,P=0.049)、产甲烷短杆菌属(OR=1.274,95%CI:1.001-1.621,P=0.049)、罗氏菌属(OR=1.429,95%CI:1.015-2.013,P=0.041)的丰度升高,会增加患者骨质疏松性骨折的风险;②拟杆菌纲(OR=0.660,95%CI:0.455-0.959,P=0.029)、拟杆菌目(OR=0.660,95%CI:0.455-0.959,P=0.029)、克里斯滕森氏菌科(OR=0.725,95%CI:0.529-0.995,P=0.047)、瘤胃球菌科(OR=0.643,95%CI:0.443-0.933,P=0.020)、肠杆菌属(OR=0.558,95%CI:0.395-0.788,P=0.001)、直肠真杆菌属(OR=0.631,95%CI:0.435-0.916,P=0.016)、毛螺菌科-UCG008 (OR=0.738,95%CI:0.546-0.998,P=0.048)、瘤胃梭菌属-9(OR=0.492,95%CI:0.324-0.746,P=0.001)的丰度升高,会降低患者骨质疏松性骨折的风险。③文章通过孟德尔随机化方法发现了16种与骨质疏松性骨折相关的肠道菌群,即以肠道菌群为暴露因素,骨质疏松性骨折为结局变量,8种肠道菌群与骨质疏松性骨折呈正向因果关联,另外8种肠道菌群与骨质疏松性骨折呈负向因果关联。④此研究结果不仅为临床上骨质疏松性骨折的早期预测及潜在治疗靶点确定了新的生物标志物,还为骨组织工程中研究通过肠道菌群改善骨质疏松性骨折的发生与预后提供了实验基础和理论依据。
https://orcid.org/0009-0007-2093-2015(赵文生);https://orcid.org/0009-0006-7762-012X(何川);https://orcid.org/0009-0009-3423-0836(李孝林)

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, 肠道菌群, 骨质疏松性骨折, 因果关系, 遗传学, 全基因组关联研究, 单核苷酸多态性, 工具变量, 风险因素

Abstract:
BACKGROUND:
Osteoporotic fracture is the most serious complication of osteoporosis. Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture, but the causal relationship between the two is unclear.
OBJECTIVE: To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. 
METHODS: The genome-wide association study (GWAS) datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9, respectively. Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable, Mendelian randomization analyses with random-effects inverse variance weighted, MR-Egger regression, weighted median, simple model, and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture. Sensitivity analyses were performed to test the reliability and robustness of the results. Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses.
RESULTS AND CONCLUSION: The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture. Elevated abundance of Actinomycetales [odds ratio (OR)=1.562, 95% confidence interval (CI): 1.027-2.375, P=0.037), Actinomycetaceae (OR=1.561, 95% CI: 1.027-2.374, P=0.037), Actinomyces (OR =1.544, 95% CI: 1.130-2.110, P=0.006), Butyricicoccus (OR=1.781, 95% CI: 1.194-2.657, P=0.005), Coprococcus 2 (OR=1.550, 95% CI: 1.068-2.251, P=0.021), Family XIII UCG-001 (OR=1.473, 95% CI: 1.001-2.168, P=0.049), Methanobrevibacter (OR=1.274, 95% CI: 1.001-1.621, P=0.049), and Roseburia (OR=1.429, 95% CI: 1.015-2.013, P=0.041) would increase the risk of osteoporotic fractures in patients. Elevated abundance of Bacteroidia (OR=0.660, 95% CI: 0.455-0.959, P=0.029), Bacteroidales (OR=0.660, 95% CI: 0.455-0.959, P=0.029), Christensenellacea (OR=0.725, 95% CI: 0.529-0.995, P=0.047), Ruminococcaceae (OR=0.643, 95% CI: 0.443-0.933, P=0.020), Enterorhabdus (OR=0.558, 95% CI: 0.395-0.788, P=0.001), Eubacterium rectale group (OR=0.631, 95% CI: 0.435-0.916, P=0.016), Lachnospiraceae UCG008 (OR=0.738, 95% CI: 0.546-0.998, P=0.048), and Ruminiclostridium 9 (OR=0.492, 95% CI: 0.324-0.746, P=0.001) would reduce the risk of osteoporotic fractures in patients. We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method. That is, using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable, eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture. The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice, but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

Key words: Mendelian randomization, gut microbiota, osteoporotic fractures, causality, genetics, genome-wide association study, single nucleotide polymorphism, instrumental variable, risk factor

中图分类号: