山东大学耳鼻喉眼学报 ›› 2025, Vol. 39 ›› Issue (5): 49-60.doi: 10.6040/j.issn.1673-3770.0.2025.144

• 论著 • 上一篇    

基于孟德尔随机化的肠道菌群与慢性鼻窦炎鼻息肉的因果关系及代谢物中介研究

张家齐1,2,袁野1,2,洪陈3,顾敏4,程雷2,5,6,陆美萍1,2   

  1. 过敏)科, 江苏 南京 210029;
    6.南京医科大学 国际变态反应研究中心, 江苏 南京 210029
  • 发布日期:2025-09-19
  • 通讯作者: 陆美萍. E-mail:lmp@njmu.edu.cn
  • 基金资助:
    国家自然科学基金(82471187);江苏省基础研究专项资金(软科学研究)项目(BK20241988);江苏省科教能力提升工程(JSDW202203)

Mendelian randomization study of gut microbiota, chronic sinusitis, and nasal polyps: Causal relationships and metabolite-mediated effects

ZHANG Jiaqi1,2, YUAN Ye1,2, HONG Chen3, GU Min4, CHENG Lei2,5,6, LU Meiping1,2   

  1. 1. Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu, China2. Clinical Allergy Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu, China3. Department of Otorhinolaryngology, The Third the People's Hospital of Bengbu/ Central Hospital of Bengbu, Bengbu 233000, Anhui, China4. Department of Otorhinolaryngology & Head and Neck Surgery, BenQ Hospital (BenQ Medical Center)Affiliated with Nanjing Medical University, Nanjing 210029, Jiangsu, China5. Department of Allergology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu, China6. International Centre for Allergy Research, Nanjing Medical University, Nanjing 210029, Jiangsu, China
  • Published:2025-09-19

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摘要： 目的 本研究旨在通过孟德尔随机化(mendelian randomization, MR)分析,探讨肠道菌群与慢性鼻窦炎(chronic sinusitis, CRS)及鼻息肉之间的因果关联,并评估代谢物在其中的中介作用。 方法 基于MiBioGen联盟的肠道菌群基因型数据和FinnGen、UK Biobank的GWAS数据,筛选工具变量,采用逆方差加权法(inverse variance weighting, IVW)、MR-Egger回归和加权中位数法(weighted median, WM)评估因果效应。通过Cochran's Q检验、MR Egger法、MR-PRESSO检验和留一法进行敏感性分析,并使用两步法MR中介分析探讨代谢物的中介作用。多变量MR被用于评估端粒长度对双歧杆菌相关菌群与CRS及鼻息肉关联的影响。 结果 肠道菌群与CRS及鼻息肉的MR分析共鉴定出7种与CRS显著相关的肠道菌群和8种与鼻息肉相关的菌群(PFDR<0.05)。代谢物及通路分析发现涉及氨基酸代谢、糖类与能量代谢、脂类与类固醇代谢、短链脂肪酸代谢、胆汁酸代谢的多种代谢产物。中介分析确认了4 组“菌群-代谢物-疾病”因果关系。同时,多变量 MR 分析显示,端粒长度的加入使双歧杆菌属和放线菌门对 CRS 的因果效应不再有统计学意义。最终,本研究发现Family_XIII_UCG-001属(genus.FamilyXIIIUCG001)通过调节N-α-乙酰鸟氨酸降低CRS的风险(4.81%),而脱硫弧菌目(order.Desulfovibrionale)通过促进肉碱相关代谢过程对鼻息肉起保护作用(6.5%)。 结论 肠道菌群与 CRS 及其表型之间存在复杂因果关系,代谢物在其中起重要中介作用,本研究为 CRS 的发病机制研究提供了新的视角。

关键词: 肠道菌群, 鼻窦炎, 鼻息肉, 孟德尔随机化, 循环代谢物

Abstract: Objective This study aimed to explore the causal relationships between gut microbiota and chronic rhinosinusitis(CRS)or nasal polyps(NP)using Mendelian randomization(MR)analysis and to assess the mediating role of circulating metabolites. Methods Instrumental variables(IVs)were selected based on gut microbiota genotype data from the MiBioGen consortium and GWAS data from FinnGen and UK Biobank. Causal effects were evaluated using inverse variance weighting(IVW), MR-Egger regression, and weighted median(WM)methods. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Metabolite-mediated pathways were investigated using two-step MR mediation analysis. Multivariable MR was also applied to evaluate the impact of telomere length on the associations between Bifidobacterium-related microbiota and CRS or NP. Results The MR analysis revealed seven gut microbial taxa significantly associated with CRS and eight associated with NP(PFDR<0.05). Metabolite and pathway analyses identified key metabolic processes, including amino acid metabolism, carbohydrate and energy metabolism, lipid and steroid metabolism, short-chain fatty acid metabolism, and bile acid metabolism. Mediation analysis confirmed four causal pathways involving microbiota, metabolites, and diseases. Additionally, multivariable MR demonstrated Additionally, multivariable MR demonstrated that adjusting for telomere length attenuated the causal effects of the genus Bifidobacterium and phylum Actinobacteria on CRS, rendering them non-significant. Notably, the genus Family_XIII_UCG-001 was observed to reduce CRS risk by modulating N-α-acetylornithine(mediation proportion: 4.81%), while the order Desulfovibrionales exhibited protective effects on NP through carnitine-related metabolism(mediation proportion: 6.50%). Conclusion There is a complex causal relationship between the gut microbiota and CRS and its phenotypes, with metabolites playing an important mediating role. This study provides a new perspective on the pathogenesis of CRS.

Key words: Gut microbiota, Chronic rhinosinusitis, Nasal polyps, Mendelian randomization, Circulating metabolites

中图分类号: 

  • R765.4+1
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