Causal relationship between kidney stones and gut microbiota contributes to the gut-kidney axis: a two-sample Mendelian randomization study.

Background: Gut microbiota, particularly , has been previously reported to be associated with kidney stones. However, the conflicting results from both observational and intervention studies have created substantial uncertainty regarding the contribution of to the formation of kidney stone.

Methods: We employed a two-sample MR analysis to investigate the causal relationship between gut microbiota and kidney stones using GWASs summary statistics obtained from the MiBioGen and FinnGen consortia. Moreover, we conducted a reserve MR analysis to assess the direction of the causal associations between gut microbiota and kidney stones. The inverse variance weighted (IVW) approach represents the primary method of Mendelian Randomization (MR) analysis.

Results: Our analyses do not yield supportive evidence for a causal link between the genus r (OR = 0.99, 95% CI: 0.90-1.09, = 0.811) and the formation of kidney stones. The order (OR = 0.79, 95% CI: 0.65-0.96, = 0.020), family (OR = 0.79, 95% CI: 0.65-0.96, = 0.019), family (OR = 0.80, 95% CI: 0.67-0.96, = 0.015), genus (OR = 0.81, 95% CI: 0.67-0.98, = 0.030) and genus (OR = 0.86, 95% CI: 0.74-0.99, = 0.040) had protective effects on kidney stones, and the genus (OR = 1.16, 95% CI: 1.01-1.33, = 0.032), genus (OR = 1.38, 95% CI: 1.04-1.84, = 0.028), genus (OR = 1.27, 95% CI: 1.06-1.52, = 0.009) were risk factors for kidney stones. Differential abundance analysis provide no evidence of a association between and kidney stones, and showed genus Subdoligranulum were risk factors for kidney stones. Reverse MR analysis did not indicate any causal association of kidney stones on gut microbiota. No considerable heterogeneity of instrumental variables or horizontal pleiotropy was observed.

Conclusion: Our two-sample MR study did not find any causal relationship between genus and kidney stones. The association between gut microbiota and kidney stones does not solely depend on the presence of genus /. A more integrated approach using multiple omics platforms is needed to better understand the pathogenesis of kidney stones in the context of complex gene-environment interactions over time.