Assessing the Relationship Between Gut Microbiota and Kidney Stones: A Two-Sample Mendelian Randomization Analysis

Increasing evidence suggests that gut microbiota are associated with the risk of kidney stone disease; however, whether a causal relationship exists remains unclear. We used Mendelian randomization to assess the potential causal relationship between gut microbiota and kidney stone disease risk.

Genetic instrumental variables for gut microbiota were identified from a genome-wide association study of 18,340 participants. Summary statistics for kidney stone disease were derived from genome-wide association studies, including 284,598 cases and 480,873 controls. The inverse-variance weighted method was used as the primary analysis. To test the robustness of the results, we further performed the weighted-median method, MR-Egger regression, and the MR pleiotropy residual sum and outlier test. Finally, reverse Mendelian randomization analysis was performed to evaluate the possibility of reverse causation.

We identified suggestive associations between 4 bacterial traits and the risk of kidney stone disease: class Lentisphaeria (odds ratio: 0.82; 95% confidence interval: 0.69-0.98; P = .032), genus Oscillibacter (odds ratio: 0.79; 95% confidence interval: 0.66-0.96; P = .018), order Victivallales (odds ratio: 0.82; 95% confidence interval: 0.68-0.98; P = .034), and genus Olsenella (odds ratio: 1.26; 95% confidence interval: 1.03-1.53; P = .022). The results of sensitivity analyses for these bacterial traits were consistent. We did not find statistically significant associations between kidney stone disease and these 4 bacterial traits in the reverse analysis.

This systematic analysis provides evidence supporting a potential causal relationship between 4 gut microbiota taxa and kidney stone disease risk. Further studies are needed to determine how gut microbiota influence kidney stone disease development.