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Research Article: Therapeutic response to exclusive enteral nutrition correlates with suppressed IL-17 signaling activity and diminished IL-1? secretion in pediatric Crohn's disease

Date Published: 2026-09-14

Abstract:
To identify molecular correlates associated with therapeutic outcomes of exclusive enteral nutrition (EEN) in pediatric Crohn's disease (PCD). This prospective observational cohort study recruited 27 treatment-naive pediatric patients with endoscopically active PCD. Intestinal mucosal tissues were collected via endoscopy at baseline and after EEN treatment. RNA sequencing, principal component analysis (PCA), protein–protein interaction (PPI) analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to identify and validate differentially expressed genes (DEGs). Patients were classified into mucosal healing [MH, Simple Endoscopic Score for Crohn's Disease (SES-CD) < 3, n = 13] and non-mucosal healing (NMH, SES-CD ? 3 with ulcers, n = 14) groups according to post-treatment SES-CD. PCA revealed partial transcriptomic segregation between the MH and NMH groups after EEN. Bioinformatic enrichment analysis identified the IL-17 signaling pathway as the most significantly enriched pathway, encompassing nine core DEGs. Integrated qRT-PCR validation and PPI network analysis pinpointed IL-1? as the key target gene. Correlation analysis demonstrated that intestinal mucosal IL-1? expression was moderately and positively correlated with SES-CD scores ( P = 0.001, r = 0.42, 95% CI: 0.17–0.63), Lewis scores ( P < 0.001, r = 0.65, 95% CI: 0.41–0.79), and weighted Pediatric Crohn's Disease Activity Index (wPCDAI) values ( P < 0.001, r = 0.51, 95% CI: 0.26–0.69). Moreover, compared with the NMH group, the MH group exhibited lower mucosal expression levels of IL-17A [MH: 0.50 (1.42) vs. NMH: 2.58 (2.05), P = 0.03], IL-17RA (MH: 0.95 ± 0.37 vs. NMH: 1.34 ± 0.53, P = 0.04), and IL-17RB [MH: 1.18 (0.54) vs. NMH: 1.64 (1.32), P < 0.01] after EEN treatment. EEN attenuates intestinal inflammation in PCD, and this therapeutic response may associate with suppressed IL-17 signaling activity and reduced IL-1? secretion.

Introduction:
To identify molecular correlates associated with therapeutic outcomes of exclusive enteral nutrition (EEN) in pediatric Crohn's disease (PCD).

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