Collagen expression downregulation and intestinal barrier impairment are associated with severe clinical phenotypes in very early-onset inflammatory bowel disease

BACKGROUND: The global incidence of pediatric inflammatory bowel disease (IBD) is increasing steadily. Children with IBD under 6 years present unique clinical characteristics. OBJECTIVE: To compare very early-onset IBD (VEO-IBD) and late-onset IBD (LO-IBD) across clinical, endoscopic, and transcriptomic profiles. METHODS: We retrospectively analyzed clinical data from 76 children (2010-2025) and leveraged the transcriptomic dataset GSE57945 (20 VEO-IBD vs. 260 LO-IBD). RESULT: VEO-IBD patients showed significantly higher rates of hematochezia (RR=1.552, 95% CI:1.099~2.191, P=0.032), fever (RR=1.696, 95% CI:1.093~2.631, P=0.034), decreased serum creatinine (RR=1.588, 95% CI:1.251~2.016, P=0.004), and higher Mayo scores (t=2.232, 95% CI:1.852~3.407, P=0.030). Transcriptomics revealed significant downregulation of collagen genes (COL12A1, COL1A1, COL7A1) in VEO-IBD, confirmed by qRT-PCR. CONCLUSION: VEO-IBD exhibits a more aggressive phenotype than LO-IBD, which may be associated with distinct clinical severity and collagen-related barrier dysfunction. These findings suggest a novel pathophysiological hypothesis linking extracellular matrix impairment to disease severity in VEO-IBD.