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

Area of Science:

• Urology
• Molecular Biology
• Microbiology

Background:

• Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) presents as Hunner lesion (HIC) and non-Hunner lesion (NHIC) subtypes.
• Distinct clinical features exist, but underlying pathogenic mechanisms for BPS/IC subtypes are poorly understood.

Purpose of the Study:

• To differentiate NHIC and HIC using multi-omics analysis.
• To uncover distinct microbiome, metabolome, and transcriptome profiles for each BPS/IC subtype.
• To elucidate unique pathogenic mechanisms driving NHIC and HIC.

Main Methods:

• Integrated multi-omics analysis (genomics, metabolomics, transcriptomics) of bladder tissue and urine samples from NHIC and HIC patients.
• High-throughput sequencing for data acquisition.
• Pathway enrichment analysis to identify differentially expressed genes, metabolites, and microbial communities.

Main Results:

• NHIC showed a predominance of Lactobacillus and Enterococcus, while HIC had higher levels of Pseudomonas and Gardnerella in urinary microbiota.
• Metabolomic analysis revealed altered arginine/proline metabolism in NHIC and steroid hormone biosynthesis in HIC.
• Transcriptomic profiling indicated upregulated immune response and viral infection pathways in HIC, contrasting with metabolic/energy pathways in NHIC.

Conclusions:

• Multi-omics analysis revealed distinct pathogenic signatures for NHIC and HIC.
• HIC pathogenesis may involve chronic immune dysregulation and past infections.
• NHIC pathogenesis appears more closely associated with metabolic disturbances, suggesting tailored therapeutic strategies for BPS/IC subtypes.