中国实用口腔科杂志 ›› 2025, Vol. 18 ›› Issue (1): 67-74.DOI: 10.19538/j.kq.2025.01.011

• 论著 • 上一篇    下一篇

基于孟德尔随机化分析肠道菌群对龋病的影响研究

王雅欣,胡    丽,乔    梁,周丽群,赵佳佳   

  1. 华中科技大学同济医学院附属协和医院口腔科,口腔颌面发育与再生湖北省重点实验室,湖北 武汉 430022;华中科技大学同济医学院口腔医学院,湖北 武汉 430030
  • 出版日期:2025-01-30 发布日期:2025-01-30
  • 基金资助:
    国家自然科学基金青年科学基金项目(81700946);湖北省自然科学基金(2024AFB1007);2022年研究生教育教学改革项目(F015010042230602806)

  • Online:2025-01-30 Published:2025-01-30

摘要: 目的    采用孟德尔随机化分析肠道菌群对龋病的影响,为制定龋病防治策略提供参考依据。方法    研究于2024年1—3月在华中科技大学同济医学院口腔医学院进行。肠道菌群全基因组关联研究(genome-wide association studies,GWAS)数据来自MiBioGen联盟的一项研究,选取与196种肠道菌群显著相关的单核苷酸多态性作为工具变量;在IEU数据库中提取与龋病相关的GWAS汇总数据作为结果,包括finn-b-K11_CARIES、ukb-b-4770和ukb-d-K02数据集。应用随机效应逆方差加权法(inverse variance-weighted,IVW)研究肠道菌群和龋病之间的因果效应,以MR-Egger和加权中位数(weighted median,WM)分析作为补充分析方法,并应用Cochran Q检验和MR-Egger截距检验进行敏感性分析。结果    IVW分析结果显示,22种肠道菌群可能与龋病相关。其中,Family[]科、韦荣球菌科、克里斯滕菌科、瘤胃球菌科、瘤胃球菌UCG014属、霍华德菌属和埃希菌属-志贺菌属可能是龋病的潜在保护因素(均OR < 1,P < 0.05);另外15种肠道菌群(广域古菌门、丹毒丝菌纲、肠杆菌目、巴斯德菌目、丹毒丝菌目、毛螺菌科、巴斯德菌科、肠杆菌科、理研菌科、丹毒丝菌科、草酸杆菌属、短真杆菌属、土生孢杆菌属、消化球菌属和座便单胞菌属)可能是龋病发生的危险因素(均OR < 1,P < 0.05)。以上22种肠道菌群经WM和MR-Egger分析发现,差异均无统计学意义(均P > 0.05)。敏感性分析结果显示,与龋病相关的22种肠道菌群未检测到异质性和水平多效性(均P > 0.05)。结论    肠道菌群可能对龋病具有双重作用影响,既可作为保护因素,也可能增加龋病发生风险,其具体作用机制仍需进一步探究。

关键词: 肠道菌群, 龋病, 孟德尔随机化分析

Abstract: Objective    To investigate the effects of gut microbiota on dental caries using Mendelian randomization analysis,providing a reference for developing prevention and treatment strategies for dental caries. Methods    This study was conducted from January 2024 to March 2024 at the School of Stomatology,Tongji Medical College,Huazhong University of Science and Technology. Genome-wide association study(GWAS)data of gut microbiota were obtained from the MiBioGen consortium,and single nucleotide polymorphism significantly associated with 196 gut microbiota taxa were selected as instrumental variables. GWAS summary data related to dental caries,including the datasets finn-b-K11_CARIES,ukb-b-4770,and ukb-d-K02,were extracted from the IEU database. The inverse variance-weighted(IVW)method was used to assess the causal effects between gut microbiota and dental caries,supplemented by MR-Egger and weighted median(WM)analyses. Sensitivity analyses were performed using Cochran Q test and MR-Egger intercept test. Results    The IVW analysis identified 22 gut microbiota taxa potentially associated with dental caries. Among them,Family[],Veillonellaceae,Christensenellaceae,Ruminococcaceae,RuminococcaceaeUCG014,Howardella,Escherichia-Shigella were potential protective factors for dental caries(all OR < 1,P < 0.05). The other 15 taxa,including Euryarchaeota,Erysipelotrichia,Enterobacteriales,Pasteurellales,Erysipelotrichales,Lachnospiraceae,Pasteurellaceae,Enterobacteriaceae,Rikenellaceae,Erysipelotrichaceae,Oxalobacter,Eubacterium brachygroup,Terrisporobacter,Peptococcus and Sellimonas were identified as possible risk factors for dental caries(all OR > 1,P < 0.05). WM and MR-Egger analyses did not reveal statistically significant differences for these 22 taxa(all P > 0.05). Sensitivity analyses showed no heterogeneity or horizontal pleiotropy among the 22 taxa associated with dental caries(all P > 0.05). Conclusion    Gut microbiota has a dual effect on dental caries,acting as both protective and risk factors. The specific mechanisms underlying these effects require further investigation.

Key words: gut microbiota, dental caries, Mendelian randomization analysis