Chaowei Fu ¹ Yu Zhao ¹ Xiang Zhou ² Jing Lv ¹ Shengkai Jin ¹ Yuhua Zhou ¹ Fengping Liu ¹ Nh Feng ^3*

• ¹ Wuxi School of Medicine, Jiangnan University, Wuxi, Liaoning Province, China
• ² Department of Urology, Jiangnan University Medical Center (Wuxi No.2 People's Hospital), Wuxi, Liaoning Province, China
• ³ Wuxi No.2 People's Hospital, Nanjing Medical University, Wuxi, China

Background: Several observational studies have indicated an association between interstitial cystitis and the composition of the gut microbiota; however, the causality and underlying mechanisms remain unclear. Understanding the link between gut microbiota and interstitial cystitis could inform strategies for prevention and treatment.A two-sample Mendelian randomization analysis was conducted using published genome-wide association study summary statistics. We employed inverse variance weighted, weighted mode, MR-Egger, weighted median, simple mode, and cML-MA methods to investigate the causal relationship between gut microbiota and interstitial cystitis. Sensitivity analysis was performed to validate the results. Relevant gut microbiota was examined through reverse MR. Single nucleotide polymorphisms were annotated using FUMA to identify genes associated with these genetic variants, thereby revealing potential host gene-microbiota associations in interstitial cystitis patients.Results: Eight bacterial taxa were identified in our analysis as associated with interstitial cystitis. Among these, Butyricimonas, Coprococcus, Lactobacillales, Lentisphaerae, and Bilophila wadsworthia were positively correlated with interstitial cystitis risk, while taxa such as Desulfovibrio piger, Oscillibacter unclassified and Ruminococcus lactaris exhibited protective effects against interstitial cystitis. The robustness of these associations was confirmed through sensitivity analyses. Reverse MR analysis did not reveal evidence of reverse causality. Single nucleotide polymorphisms were annotated using FUMA and subjected to biological analysis. Seven hub genes (SPTBN1, PSME4, CHAC2, ERLEC1, ASB3, STAT5A, and STAT3) were identified as differentially expressed between interstitial cystitis patients and healthy individuals, representing potential therapeutic targets.Our two-sample Mendelian randomization study established a causal relationship between gut microbiota and interstitial cystitis. Furthermore, our identification of a host genemicrobiota association offers a new avenue for investigating the potential pathogenesis of interstitial cystitis and suggests avenues for the development of personalized treatment strategies.