Retrospective Analysis of Melatonin Signalling Biomarkers in Paediatric Inflammatory Bowel Disease: Correlation with Disease Activity Using Structural Equation Modelling

Abstract Background: Melatonin is a potential modulator of inflammatory bowel disease (IBD) pathophysiology due to its antioxidant, anti-inflammatory and gut barrier-protective properties. However, the role and clinical significance of melatonin signalling biomarkers in paediatric IBD remains poorly understood. Methods: This retrospective study analysed key biomarkers of melatonin signalling in pediatric IBD patients and healthy controls. Measurements included serum melatonin, urinary 6-sulfatoxymelatonin and intestinal expression of melatonin receptors and key synthesis enzymes. Structural equation modelling (SEM) was employed to examine relationships between melatonin signalling, intestinal barrier function, oxidative stress levels, immune dysregulation, gut microbiota composition and IBD disease activity. Results: Paediatric IBD patients exhibited significantly lower melatonin levels and receptor expression compared to healthy controls, with progressive reduction correlating strongly with increasing disease severity ( P < 0.001). SEM analysis revealed that melatonin signalling influenced IBD activity through multiple pathways: directly (β = −0.22, P = 0.003) and indirectly through disruptions in intestinal barrier integrity (β = −0.15), oxidative stress (β = −0.11), immune regulation (β = −0.11) and gut microbiota (β = −0.08). These effects were more pronounced in younger patients with poor sleep quality. Conclusion: Melatonin signalling biomarkers show promise as both diagnostic indicators and therapeutic targets in pediatric IBD. The identified pathways suggest that melatonin supplementation could simultaneously address multiple disease mechanisms. Future clinical trials should evaluate melatonin’s efficacy as an adjunct therapy in paediatric IBD management.