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

doi:10.6040/j.issn.1673-3770.0.2025.144

Abstract

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(P_FDR<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

CLC Number:

R765.4+1

ZHANG Jiaqi, YUAN Ye, HONG Chen, GU Min, CHENG Lei, LU Meiping. Mendelian randomization study of gut microbiota, chronic sinusitis, and nasal polyps: Causal relationships and metabolite-mediated effects[J].Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(5): 49-60.

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

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