AUTHOR=Zhang Ruiqiao , Zhao Weijie , Zhao Ruijie , Zhao Yunhai , Zhang Yanlong , Liang Xuezhi 

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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1170793

DOI=10.3389/fmicb.2023.1170793

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>IVW results confirmed that class <italic>Deltaproteobacteria</italic> (OR = 0.814, 95% CI: 0.666–0.995, <italic>P</italic> = 0.045), order <italic>NB1n</italic> (OR = 0.833, 95% CI: 0.737–0.940, <italic>P</italic> = 3.15 × 10<sup>−3</sup>), family <italic>Clostridiaceae1</italic> (OR = 0.729, 95% CI: 0.581–0.916, <italic>P</italic> = 6.61 × 10<sup>−3</sup>), genus <italic>Barnesiella</italic> (OR = 0.695, 95% CI: 0.551–0.877, <italic>P</italic> = 2.20 × 10<sup>−3</sup>), genus <italic>Clostridium sensu_stricto_1</italic> (OR = 0.777, 95% CI: 0.612–0.986, <italic>P</italic> = 0.0380), genus <italic>Flavonifractor</italic> (OR = 0.711, 95% CI: 0.536–0.944, <italic>P</italic> = 0.0181), genus <italic>Hungatella</italic> (OR = 0.829, 95% CI: 0.690–0.995, <italic>P</italic> = 0.0444), and genus <italic>Oscillospira</italic> (OR = 0.758, 95% CI: 0.577–0.996, <italic>P</italic> = 0.0464) had a protective effect on upper urinary urolithiasis, while <italic>Eubacterium xylanophilum</italic> (OR =1.26, 95% CI: 1.010–1.566, <italic>P</italic> = 0.0423) had the opposite effect. Sensitivity analysis did not find outlier SNPs.</p></sec><sec><title>Conclusion</title><p>In summary, a causal relationship was found between several genera and upper urinary urolithiasis. However, we still need further randomized controlled trials to validate.</p></sec>