Causal effects of gut microbiota on the risk of urinary tract stones: A bidirectional two-sample mendelian randomization study

Background: Recent studies increasingly suggest notable changes in both the quantity and types of gut microbiota among individuals suffering from urinary tract stones. However, the causal relationship between GMB and urinary tract stone formation remains elusive, which we aim to further investigate in this research through Mendelian Randomization (MR) analysis. Materials and methods: Single nucleotide polymorphisms (SNPs) associated with the human GMB were selected from MiBioGen International Consortium GWAS dataset. Data on urinary tract stone-related traits and associated SNPs were sourced from the IEU Open GWAS database. To investigate the causal relationships between gut microbiota and urinary tract stones, Mendelian Randomization (MR) was applied using genetic variants as instrumental variables, utilizing a bidirectional two-sample MR framework. This analysis incorporated various statistical techniques such as inverse variance weighting, weighted median analysis, MR-Egger, and the maximum likelihood method. To ensure the reliability of the findings, a range of sensitivity tests were conducted, including Cochran's Q test, the MR-Egger intercept, leave-one-out cross-validation, and examination of funnel plots. Results: The results revealed the causal relationship between the increase in the abundance of 10 microbial taxa, including Genus-Barnesiella (IVW OR = 0.73, 95%CI 0.73-0.89, P = 2.29 x 10-3) and Genus-Flavonifractor (IVW OR = 0.69, 95%CI 0.53-0.91, P = 8.57 x 10-3), and the decreased risk of urinary tract stone formation. Conversely, the development of urinary tract stones was observed to potentially instigate alterations in the abundance of 13 microbial taxa, among which Genus-Ruminococcus torques group was notably affected (IVW OR = 1.07, 95%CI 0.64-0.98, P = 1.86 x 10-3). In this context, Genus-Clostridium sensustricto1 exhibited a bidirectional causal relationship with urinary tract stones, while the remaining significant microbial taxa demonstrated unidirectional causal effects in the two-sample MR analysis. Sensitivity analyses did not identify significant estimates of heterogeneity or pleiotropy. Conclusion: To summarize, the results of this study suggest a likely causative link between gut microbiota and the incidence of urinary tract stones. This insight opens up potential pathways for discovering biomarkers and therapeutic targets in the management and prevention of urolithiasis. However, further in-depth research is warranted to investigate these associations.