中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (20): 4369-4378.doi: 10.12307/2025.689

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

椎间盘退行性变与473种肠道菌群的关系：芬兰数据库大数据信息可借鉴的意义

王梓焜1，李树栋2，高  泷1，范书豪1，李  城3，孟纯阳4   

  1. 1山东第一医科大学(山东省医学科学院)，山东省济南市  250117；2山东中医药大学第一临床医学院，山东省济南市  250355；3济宁医学院临床医学院，山东省济宁市  272067；4济宁医学院附属医院脊柱外科，山东省济宁市  272000
  • 收稿日期:2024-08-01 接受日期:2024-09-09 出版日期:2025-07-18 发布日期:2024-12-25
  • 通讯作者: 孟纯阳，医学博士，主任医师，博士生导师，济宁医学院附属医院脊柱外科，山东省济宁市 272000
  • 作者简介:王梓焜，男，1998年生，山东省潍坊市人，汉族，山东第一医科大学(山东省医学科学院)在读硕士，主要从事脊柱相关疾病的研究。
  • 基金资助:
    国家自然科学基金面上项目(82372477)，项目负责人：孟纯阳；山东省自然科学基金重点项目(ZR2020KH010)，项目负责人：孟纯阳

Relationship between intervertebral disc degeneration and 473 gut microbiotas: what can be learned from big data information in the FinnGen database

Wang Zikun1, Li Shudong2, Gao Shuang1, Fan Shuhao1, Li Cheng3, Meng Chunyang4   

  1. 1Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan 250117, Shandong Province, China; 2First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; 3College of Clinical Medicine, Jining Medical University, Jining 272067, Shandong Province, China; 4Department of Spine Surgery, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China
  • Received:2024-08-01 Accepted:2024-09-09 Online:2025-07-18 Published:2024-12-25
  • Contact: Meng Chunyang, MD, Chief physician, Doctoral supervisor, Department of Spine Surgery, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China
  • About author:Wang Zikun, Master’s candidate, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan 250117, Shandong Province, China
  • Supported by:
    The National Natural Science Foundation of China (General Program), No. 82372477 (to MCY); Shandong Province Natural Science Foundation (Key Project), No. ZR2020KH010 (to MCY)

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摘要：



文题释义：
孟德尔随机化：是一种广泛使用的流行病学研究方法。作为一种基于遗传变异的因果推断方法，其利用单核苷酸多态性作为工具变量，以评估暴露因素与结局变量之间的因果关系。该方法很好地避免了在观察性研究和随机对照研究中容易出现的混杂因素，避免偏倚和反向因果关系的混淆。
肠道菌群：是指栖息在肠道中并与宿主生物体(包括细菌、原生动物、真菌、古细菌和病毒)共存的不同微生物种群。它们与宿主的身体和外部环境之间形成了一个相互依存的微生态系统，其组成以及多样性可影响多种生理过程，与人类健康息息相关。

背景：有研究表明，调节肠道菌群可能会影响椎间盘退变的进程。然而，肠道菌群与椎间盘退变的因果关系尚不清楚。
目的：采用孟德尔随机化方法来评估肠道菌群与椎间盘退变之间的潜在因果关系。
方法：应用公开发表最新的473种肠道菌群的全基因组关联分析汇总统计数据和芬兰数据库R11中的椎间盘退变的全基因组关联分析汇总数据(椎间盘退变病例46 205例和对照组322 314例)。采用逆方差加权法、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椎间盘退变之间的因果关系。敏感性分析用于检验孟德尔随机化分析结果是否可靠。反向孟德尔随机化以全部肠道菌群作为结局进行效应分析和敏感性分析。
结果与结论：①正向孟德尔随机化的逆方差加权法结果显示，毛螺菌目，UBA-6960科、嗜热厌氧杆菌科、盐单胞菌科、丛毛单菌属、戈登氏菌属和欧陆森氏菌属与椎间盘退变呈现正相关。短螺旋体目、假单胞菌目、短螺旋菌科、CAG-776属、螺杆菌属、CAG-448种sp003150135、CAG-776种sp000438195、布劳特氏菌种-A sp000285855和汉逊布劳氏菌种与椎间盘退变呈现负相关。②反向孟德尔随机化结果显示，椎间盘退变与玫瑰巴氏菌属、地电细菌属C、弗氏埃希菌种、弗氏丙酸杆菌种、UBA-1777种sp900319835、铜绿假单胞菌种和韦氏芽孢杆菌种呈正相关，与明串珠菌属、普雷沃氏菌种sp000434975、布劳特氏菌种-A sp000285855、CAG-194种sp002441865和CAG-590种sp000431135呈负相关。③双向敏感性分析均未发现存在异质性或水平多效性。④上述结果说明，基于芬兰数据库探究肠道菌群与椎间盘退变的因果关系，为临床上椎间盘退变的早期预测及治疗探索了新的生物标志物。另外，对于中国生物医学研究，可以借鉴建立大型数据库，整合多中心的医疗数据，为肠道菌群与椎间盘退变关系的研究提供坚实基础，与其他国家的科研团队加强交流与合作，共同推动肠道菌群与疾病关系的研究，为全球医学发展作出贡献。
https://orcid.org/0009-0007-5906-0613(王梓焜)；https://orcid.org/0000-0002-3334-9503(孟纯阳)

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, 椎间盘退变, 肠道菌群, 全基因组关联分析, 单核苷酸多态性 , 逆方差加权法, 水平多效性, 敏感性分析

Abstract: BACKGROUND: Some research has suggested that regulation of gut microbiota may influence the course of intervertebral disc degeneration. However, the causal relationship of gut microbiota on intervertebral disc degeneration is unknown. 
OBJECTIVE: To assess the potential causal relationship between gut microbiota and intervertebral disc degeneration using a Mendelian randomization method.
METHODS: Genome-wide association analysis summary statistics for 473 gut microbiota and genome-wide association analysis summary data for intervertebral disc degeneration from the R11 of the FinnGen database (46 205 cases of intervertebral disc degeneration and 322 314 controls) from the most recent publicly available publication were applied. Inverse variance weighting, MR-Egger regression, weighted median, weighted modeling, and simple modeling were used to investigate the causal relationship between gut microbiota and intervertebral disc degeneration. Sensitivity analyses were used to test whether the results of Mendelian randomization analyses were reliable. Reverse Mendelian randomization was performed with all gut microbiota as the outcomes for effect analysis and sensitivity analysis.
RESULTS AND CONCLUSION: (1) The results of the inverse variance weighting method of the forward Mendelian randomization method showed that the order Trichosporonaceae, the family UBA-6960, the family Anaerobes thermophilus, the family Salmonellaceae, the genus Pseudomonas tufts, the species Gordonella and the species Euclidia showed a positive correlation with intervertebral disc degeneration. The order Spirochaetes, the order Pseudomonas, the family Spirochaetaceae, the genus CAG-776, the genus Helicobacter, the species CAG-448 sp003150135, the species CAG-776 sp000438195, the species Brautella -A sp000285855 and the species Hanson’s Brautella showed a negative correlation with intervertebral disc degeneration. (2) The results of reverse Mendelian randomization showed that intervertebral disc degeneration was positively correlated with the genus Bartonella rosea, the genus Geobacillus C, the species Escherichia fumigatus, the species Propionibacterium fumigatus, the species UBA-1777 sp900319835, the species Pseudomonas aeruginosa and the species Bacillus subtilis, while negatively correlated with the species Streptomyces mingoldii, the species Prevotella sp000434975, the species Brault’s A sp000285855, the species CAG-194 sp002441865 and the species CAG-590 sp000431135. (3) No heterogeneity or horizontal pleiotropy was found in the two-way sensitivity analysis. (4) The results described above indicate that the causal relationship between gut microbiota and intervertebral disc degeneration based on the Finnish database contributes to the exploration on new biomarkers for the early prediction and treatment of intervertebral disc degeneration in clinical practice. In addition, the establishment of a large database and the integration of medical data from multiple centers can be drawn upon in biomedical research in China to provide a solid foundation for studying the relationship between gut microbiota and intervertebral disc degeneration. We will strengthen communication and cooperation with research teams in other countries to jointly promote the research on the relationship between gut microbiota and diseases and contribute to the development of global medicine.

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, intervertebral disc degeneration, gut microbiota, genome-wide association analysis, single nucleotide polymorphisms, inverse variance weighting method, horizontal pleiotropy, sensitivity analysis

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