Tryptophan Metabolism in Pediatric Atopic Dermatitis: Shared Mechanisms, Age-Specific Biomarkers, and Emerging...

Atopic dermatitis affects up to one in five children; however, most mechanistic evidence linking tryptophan metabolism to disease pathogenesis derives from adult cohorts and preclinical models. Whether these mechanisms operate similarly across pediatric developmental stages remains poorly characterized. Tryptophan metabolism, through the kynurenine, serotonin-melatonin, and microbiota-derived indole pathways, regulates immune homeostasis, epidermal barrier integrity, and gut-skin microbiome crosstalk, with disruptions implicated in pediatric and adult disease alike. This review synthesizes pediatric evidence on tryptophan metabolism in atopic dermatitis, benchmarked against the more extensive adult and preclinical literature, spanning aryl hydrocarbon receptor signaling, filaggrin regulation, gut and skin microbiome-derived metabolites, circulating biomarkers, and emerging therapeutics including tapinarof, melatonin, and dupilumab. Age-stratified evidence indicates that components of this pathway have clinical or translational feasibility in children; however, standardized, prospective studies directly contrasting age groups are still lacking. By mapping pediatric-adult differences, the review identifies mechanisms that may be shared across age groups while acknowledging the limited direct pediatric evidence, providing a hypothesis-generating framework for future age-appropriate, biomarker-informed precision medicine in pediatric atopic dermatitis (PAD).