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中国医药导刊 ›› 2025, Vol. 27 ›› Issue (6): 606-614.

• 医药信息学 • 上一篇    下一篇

基于孟德尔随机化和GWAS数据的肠道菌群与肠易激综合征的因果关系探讨

李佳灿1, 彭卓嵛2*, 李桂贤2, 李敏2, 王娜1   

  1. 1.广西中医药大学,广西 南宁 530023;2.广西中医药大学第一附属医院,广西 南宁 530023
  • 收稿日期:2024-12-05 修回日期:2025-03-11 接受日期:2025-08-05 出版日期:2025-06-28 发布日期:2025-08-06
  • 基金资助:
     国家自然科学基金(82060848);广西中医药适宜技术开发与推广(GZSY2024023);国家中医药管理局全国名老中医药专家李桂贤传承工作室建设项目(国中医药人教发〔2016〕42号)

Causal Relationship Between Intestinal Flora and Irritable Bowel Syndrome Based on Mendelian Randomization and GWAS Data

LI Jiacan1, PENG Zhuoyu2*, LI Guixian2, LI Min2, WANG Na1   

  1. 1.Guangxi University of Chinese Medicine Guangxi Nanning 530023, China
    2.The First Affiliated Hospital of Guangxi University of Chinese Medicine Guangxi Nanning 530023, China
  • Received:2024-12-05 Revised:2025-03-11 Accepted:2025-08-05 Online:2025-06-28 Published:2025-08-06
  • Supported by:
    基于互联网+探讨加味资生汤治疗脾虚型IBS-D伴SIBO的临床研究(GZSY2024023); 2024年国家中医优势专科建设项目-脾胃病科(2024010)

摘要:

目的:通过两样本、双向孟德尔随机化(MR)研究方法,分析肠道菌群与肠易激综合征(IBS)之间的因果关联,为两者发病风险因果相关性提供遗传学证据支持。方法:从GWAS数据库中分别获取肠道菌群和IBS的基因数据,筛选两者强相关的单核苷酸多态性信息作为工具变量,利用逆方差加权法(IVW)、加权模型法、MR-Egger回归法、简单模型法、加权中位数法进行双向MR分析,其中IVW为主要分析方法,随后对MR结果进行敏感性检验,以评估其可靠性和稳定性。结果:正向MR探究肠道菌群对IBS发病的因果驱动作用,瘤胃球菌科与IBS存在正向因果关系,草酸杆菌科、瘤胃球菌属UCG013组与IBS存在负向因果关系,留一法分析结果稳定,敏感性检验显示无异质性及水平多效性。反向MR验证IBS病理状态对菌群结构的反馈调节效应,IBS与瘤胃球菌科呈正向因果关系,与草酸杆菌科、瘤胃球菌属UCG013组呈负向因果关系,留一法表明结果稳定,敏感性检验提示存在异质性和水平多效性。结论:肠道菌群和IBS之间具有双向因果联系,正向MR发现瘤胃球菌科丰度升高与IBS发生风险增强相关,草酸杆菌科、瘤胃球菌属UCG013组丰度升高与IBS发生风险降低相关;反向MR发现随着IBS发生风险增强,瘤胃球菌科丰度增多,草酸杆菌科、瘤胃球菌属UCG013组丰度减少,提示存在“宿主-菌群双向互作环路”。为临床上IBS的早期预测及治疗靶点确定新的生物学标志,以及为研究肠道菌群改善IBS的发生与预后提供实验数据和理论基础。

  

关键词: 孟德尔随机化, 肠道菌群, 肠易激综合征, 因果关系

Abstract:

Objective: To analyze the causal relationship between intestinal flora and irritable bowel syndrome IBS through the two-sample bidirectional Mendelian randomization MR research method and to provide genetic evidence support for the causal correlation between the two pathogenic risks.Methods: The genetic data of intestinal flora and IBS were obtained from the GWAS database respectively and the information of single nucleotide polymorphisms that were strongly correlated between the two were screened as instrumental variables. Bidirectional MR analyses were performed using inverse variance weighting IVW), weighted modeling MR-Egger regression simple modeling and weighted median methods with IVW as the main analysis method. Subsequently sensitivity tests were performed to assess the reliability and stability of the MR results.Results: Exploring the causal driving effect of intestinal flora on the pathogenesis of IBS by forward MR the results showed positive causality between family Ruminococcaceae and IBS and negative causality with family Oxalobacteraceae genus RuminococcaceaeUCG013 and IBS and the leave-one-out method showed stable results and the sensitivity test showed no heterogeneity and horizontal pleiotropy.Reverse MR verification of the feedback regulation effect of IBS pathological state on the structure of flora the results showed a positive causal relationship between IBS and family Ruminococcaceae and a negative causal relationship with family Oxalobacteraceae genus RuminococcaceaeUCG013. The leave-one-out method showed stable results and the sensitivity analysis suggested the presence of heterogeneity and horizontal pleiotropy.Conclusion: There was a bi-directional causal link between intestinal flora and IBS with forward MR finding that increased abundance of family Ruminococcaceae was associated with enhanced risk of IBS and increased abundance of family Oxalobacteraceae genus RuminococcaceaeUCG013 was associated with a reduced risk of IBS and reverse MR finding that as the risk of IBS was enhanced the abundance of family Ruminococcaceae increased and the abundance of family Oxalobacteraceae genus RuminococcaceaeUCG013 decreased.It is suggested that there is a "host-flora" bidirectional interaction loop. This study airs to determine new biological markers for the early prediction and therapeutic targets of IBS in clinic and to provide experimental data and theoretical basis for the study of intestinal flora to reduce occurrence and improve the prognosis of IBS.


Key words:  , Mendelian randomization , Intestinal flora , Irritable bowel syndrome , Causality

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