Mendelian randomization analysis of the causal relationship between gut microbiota，plasma metabolites and upper urinary tract stones
10.3969/j.issn.1009-8291.2025.05.010
- VernacularTitle:孟德尔随机化法分析肠道菌群、血浆代谢物与上尿路结石的因果关系
- Author:
Guanwei WU
1
;
Jiawei WANG
1
;
Yingqing LIU
1
;
Heqian LIU
1
;
Zehong GAO
1
;
Haifeng YAN
1
;
Xingyu GAO
1
;
Lingsong TAO
1
Author Information
1. Department of Urology, Affiliated Wuhu Hospital of East China Normal University, Wuhu 241000, China
- Publication Type:Journal Article
- Keywords:
gut microbiota;
plasma metabolites;
upper urinary tract stones;
Mendelian randomization
- From:
Journal of Modern Urology
2025;30(5):424-431
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the causal relationship between gut microbiota and upper urinary tract stones using Mendelian randomization (MR) analysis，and to investigate the potential mediating role of plasma metabolites. Methods: Data on gut microbiota，plasma metabolites，and upper urinary tract stones were obtained from publicly available Genome-wide Association Studies (GWAS).Bidirectional MR analysis was performed to examine the causal relationship between gut microbiota and upper urinary tract stones.Subsequently，a two-step MR approach was employed to determine whether gut microbiota contribute to upper urinary tract stones through plasma metabolites，and the mediating effects and mediator ratio were calculated.The inverse variance weighted (IVW) method was used as the primary analytical tool，supplemented by Bayesian weighted Mendelian randomization (BWMR)，MR-Egger，and weighted median (WM) analyses.Horizontal pleiotropy and heterogeneity tests were conducted to ensure the robustness of the findings. Results: Bidirectional MR analysis identified causal associations between 7 gut microbial taxa and 6 microbial metabolic pathways with upper urinary tract stones，while the development of upper urinary tract stones affected 13 gut microbial taxa and 5 metabolic pathways.Additionally，43 plasma metabolites (including 27 identified metabolites，8 unidentified metabolites，and 8 metabolite ratios) were causally associated with upper urinary tract stones.The two-step MR analysis identified 11 potential causal pathways.After metabolic pathways and unidentified metabolites were excluded，a causal link mediated by Bacteroides faecis between galactarate and upper urinary tract stones was confirmed，with a mediation proportion of 16.99% (95%CI：5.76%-33.95%，P=0.0371). Conclusion: This study establishes a causal relationship between parabacteroides and upper urinary tract stones，and elucidates the mediating role of galactarate，offering new insights into the pathogenesis and prevention strategies for upper urinary tract stones.
