Causal relationship between gut microbiota and viral pneumonia and the mediating role of metabolites:a Mendelian randomization study
10.11855/j.issn.0577-7402.1870.2025.0428
- VernacularTitle:肠道微生物与病毒性肺炎的因果关系及代谢物的中介作用:孟德尔随机化研究
- Author:
Ya-Xuan DU
1
;
Han-Bing JI
;
Jie DING
;
Jia-Rui BAI
;
Xiao-Ling YANG
;
Xiao-Man GUO
;
Hai-Tao DU
Author Information
1. 沈阳药科大学中药学院,辽宁 本溪 117004
- Keywords:
gut microbiota;
viral pneumonia;
plasma metabolites;
Mendelian randomisation;
mediation analysis
- From:
Medical Journal of Chinese People's Liberation Army
2025;50(11):1398-1406
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the causal relationship between gut microbiota and viral pneumonia,as well as the underlying mechanisms,using two-sample and two-step Mendelian randomization(MR)approaches,thereby providing novel insights for the prevention and treatment of viral pneumonia.Methods All data were obtained from publicly available genome-wide association studies(GWAS)pooled datasets,including gut microbiota data from the MiBioGen Consortium and the Netherlands Microbiome Project,viral pneumonia data from the FinnGen R10 database,and plasma metabolome data from the publicly available GWAS Catalog.Instrumental variables(IVs)were extracted according to the predefined threshold values.MR analyses were conducted using inverse variance weighting(IVW),MR-Egger,weighted median(WME),weighted mode(WM),and Bayesian-weighted Mendelian randomization(BWMR)methods.Reverse MR analysis was performed to determine whether there was a reverse association.Two-step MR analysis was used to explore the potential mediating role of plasma metabolites,and a series of sensitivity analyses were performed to test the stability of the results.Results Among 196 gut microbiota taxa from the MiBioGen consortium GWAS,11 taxa were associated with viral pneumonia.An increase in the abundance of 4 taxa increased the risk of viral pneumonia,while an increase in the abundance of 7 taxa had a protective effect against viral pneumonia.Among the 207 gut microbiota taxa from the Dutch Microbiome Project GWAS data,10 taxa were associated with viral pneumonia,with 6 risk-increasing and 4 protective taxa identified.Mediation analysis results showed that the causal effect of Defluviitaleaceae on viral pneumonia(OR=0.708,95%CI 0.540-0.929,P=0.013)was mediated to some extent by the N6-acetyllysine levels,with a mediation ratio of 18.4%.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific gut microbiota are causally associated with viral pneumonia and show potential differences across different populations;the protective effect of Defluviitaleaceae against viral pneumonia may be mediated by the N6-acetyllysine levels.Targeting metabolites may become a potential therapeutic approach for viral pneumonia.
