BackgroundThe correlation between gut microbiota and interstitial cystitis has garnered significant attention in previous studies. Nevertheless, the causal relationship between them remains to be clarified.MethodsGenetic variation serves as a tool in Mendelian randomization analyses, facilitating the inference of causal relationships between exposure factors and disease outcomes. In this study, summary statistics derived from a comprehensive genome-wide association study conducted by the MiBioGen consortium were utilized as exposure factors, while interstitial cystitis data sourced from the GWAS Catalog served as the disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis.ResultsIVW results confirmed that genus Haemophilus (OR = 2.20, 95% CI: 1.16–4.15, p = 0.015), genus Butyricimonas (OR = 2.26, 95% CI: 1.15–4.45, p = 0.018), genus Bacteroides (OR = 4.27, 95% CI: 1.36–13.4, p = 0.013) and Coprococcus1 (OR = 3.39, 95% CI: 1.28–8.99, p = 0.014) had a risk effect on interstitial cystitis. Sensitivity analysis did not find outlier SNPs.ConclusionOur analysis has identified a causal relationship between specific genera and interstitial cystitis. However, further validation through randomized controlled trials is essential to substantiate these findings.