Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization

Ruiqiao Zhang; Weijie Zhao; Ruijie Zhao; Yunhai Zhao; Yanlong Zhang; Xuezhi Liang

doi:10.3389/fmicb.2023.1170793

Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization

Front Microbiol. 2023 May 18:14:1170793. doi: 10.3389/fmicb.2023.1170793. eCollection 2023.

Authors

Ruiqiao Zhang^{1

2}, Weijie Zhao², Ruijie Zhao², Yunhai Zhao², Yanlong Zhang³, Xuezhi Liang¹

Affiliations

¹ Department of Urology Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
² The First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China.
³ Department of Urology Surgery, Capital Medical University, Beijing, China.

Abstract

Background: Several reports in recent years have found an association between gut microbiota and upper urinary urolithiasis. However, the causal relationship between them remains to be clarified.

Methods: Genetic variation is used as a tool in Mendelian randomization for inference of whether exposure factors have a causal effect on disease outcomes. We selected summary statistics from a large genome-wide association study of the gut microbiome published by the MiBioGen consortium with a sample size of 18,340 as an exposure factor and upper urinary urolithiasis data from FinnGen GWAS with 4,969 calculi cases and 213,445 controls as a disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, maximum likelihood, and weighted median. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis.

Results: IVW results confirmed that class Deltaproteobacteria (OR = 0.814, 95% CI: 0.666-0.995, P = 0.045), order NB1n (OR = 0.833, 95% CI: 0.737-0.940, P = 3.15 × 10^-3), family Clostridiaceae1 (OR = 0.729, 95% CI: 0.581-0.916, P = 6.61 × 10^-3), genus Barnesiella (OR = 0.695, 95% CI: 0.551-0.877, P = 2.20 × 10^-3), genus Clostridium sensu_stricto_1 (OR = 0.777, 95% CI: 0.612-0.986, P = 0.0380), genus Flavonifractor (OR = 0.711, 95% CI: 0.536-0.944, P = 0.0181), genus Hungatella (OR = 0.829, 95% CI: 0.690-0.995, P = 0.0444), and genus Oscillospira (OR = 0.758, 95% CI: 0.577-0.996, P = 0.0464) had a protective effect on upper urinary urolithiasis, while Eubacterium xylanophilum (OR =1.26, 95% CI: 1.010-1.566, P = 0.0423) had the opposite effect. Sensitivity analysis did not find outlier SNPs.

Conclusion: In summary, a causal relationship was found between several genera and upper urinary urolithiasis. However, we still need further randomized controlled trials to validate.

Keywords: Mendelian randomization; causal relationship; gut microbiota; inverse variance weighted; renal stones; upper urinary urolithiasis.