Multi-omics profiling reveals distinct pathogenic mechanisms in Hunner and non-Hunner interstitial cystitis subtypes

Bladder Pain Syndrome/Interstitial Cystitis encompasses Hunner lesion and non-Hunner lesion (NHIC) subtypes, characterized by chronic pelvic pain and urinary symptoms. The two subtypes show distinct clinical presentations, yet their underlying mechanisms remain poorly understood. Advancements in biological detection technologies allow for deeper insights into disease pathogenesis through integrated multi-omics approaches. This study aims to delineate the differences between NHIC and HIC using multi-omics analysis to uncover distinct microbiome, metabolome, and transcriptome profiles, thereby elucidating their unique pathogenic mechanisms. We conducted a comprehensive analysis involving bladder tissue samples and urine specimens from NHIC and HIC patients. Genomic, metabolomic, and transcriptomic data were obtained using high-throughput sequencing techniques. Differentially expressed genes, metabolites, and microbial communities were identified and subjected to pathway enrichment analysis to explore their associations with disease subtypes. Our findings revealed significant differences in the urinary microbiota, with NHIC showing a predominance of Lactobacillus and Enterococcus, while HIC exhibited higher levels of Pseudomonas and Gardnerella. Metabolomic analysis identified altered pathways, such as arginine and proline metabolism in NHIC and steroid hormone biosynthesis in HIC. Transcriptomic profiling highlighted upregulation of immune response genes in HIC, particularly those involved in mast cell degranulation and viral infection pathways. In contrast, NHIC was associated with increased expression of metabolic and energy-related pathways. This multi-omics analysis revealed distinct pathogenic signatures between NHIC and HIC, indicating that HIC may be driven by chronic immune dysregulation and past infections, while NHIC is more closely associated with metabolic disturbances. These insights suggest potential avenues for tailored therapeutic interventions based on the molecular characteristics of each subtype. Further research is warranted to confirm these findings and explore their clinical implications.