Identification of Salivary Exosome-Derived miRNAs as Potential Biomarkers for Non-Invasive Diagnosis and Proactive Monitoring of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), a chronic inflammatory disorder with relapsing/remitting characteristics, lacks reliable non-invasive biomarkers for accurate diagnosis and longitudinal monitoring. This study explored salivary exosomal miRNAs as potential biomarkers to address this unmet clinical need. Using discovery (24 IBD patients [11 active, 13 remission] and 6 healthy controls [HCs]) and validation cohorts (102 IBD patients [53 active, 49 remission] and 18 HCs), we analyzed miRNA profiles via reverse transcription quantitative PCR (RT-qPCR). Receiver operating characteristic (ROC) curves evaluated diagnostic performance, with area under the curve (AUC) quantifying discriminatory capacity. Initial screening revealed 23 miRNAs significantly upregulated in IBD salivary exosomes. An 8-miRNA signature distinguished IBD patients from HCs in validation analyses, with five miRNAs (hsa-miR-1246, hsa-miR-142-3p, hsa-miR-16-5p, hsa-miR-301a-3p, and hsa-miR-4516) showing strong correlations with disease activity. The combination of hsa-miR-16-5p and hsa-miR-4516 achieved robust discrimination (AUC = 0.925 for IBD vs. HCs; AUC = 0.82 for active disease vs. remission). A composite model integrating all five miRNAs demonstrated superior performance (AUC = 1.00 for IBD/HC differentiation; AUC = 0.86 for disease activity assessment). These findings reveal dynamic associations between salivary exosomal miRNA signatures and IBD progression, underscoring their utility as non-invasive diagnostic tools. This approach enables serial sampling, enhances patient compliance, and provides actionable insights for personalized disease management, establishing salivary exosomal miRNAs as promising candidates for clinical translation in IBD care.