Fecal microRNA signatures as non‐invasive diagnostic and prognostic markers of pediatric inflammatory bowel diseases

OBJECTIVES: The identification of novel noninvasive diagnostic and prognostic biomarkers for pediatric inflammatory bowel disease (PIBD), including pediatric Crohn's disease (pCD) and ulcerative colitis (pUC), is crucial for improving therapeutic outcomes. Given their involvement in PIBD pathogenesis, microRNAs (miRNAs) represent promising candidates. This study investigates their potential diagnostic value and clinical utility. METHODS: The study involved 81 treatment-naive PIBD patients and 30 non-IBD controls from whom stool samples were collected. Fecal microRNA analysis was performed using small RNA next-generation sequencing. Differentially expressed miRNAs (DEMs) were identified in the exploratory phase (34 PIBD, 20 non-IBD children). Logistic regression was used to establish diagnostic and prognostic miRNA expression signatures. The designed miRNA panels were validated using leave-one-out cross-validation and on an independent cohort (47 PIBD, 10 non-IBD children). RESULTS: A diagnostic signature of four fecal miRNAs (10392-5p, miR-1246, miR-4695-5p, and miR-5006-5p) distinguished pCD from non-IBD with 79.55% accuracy. Three fecal miRNAs (miR-1290, miR-3960, and miR-5006-5p) differentiated pUC from non-IBD with 78.26% accuracy. For treatment-naïve PIBD patients, panels of five and six miRNAs predicted residual disease activity at 3 months with 100% accuracy for pUC patients and 86.28% accuracy for pCD patients. Additionally, distinct signatures of four and six miRNAs predicted relapse within 12 months with accuracies of 96.87% (pUC) and 88.01% (pCD), respectively. CONCLUSION: We identified fecal miRNA expression profiles with strong diagnostic and prognostic value in PIBD. These results contribute to improved stratification of disease severity and risk, supporting the advancement of precision and personalized approaches in pediatric IBD management.