Tryptophan Metabolism at the Crossroads of Immunity, Barrier Function, and the Microbiome in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex interplay among immune imbalance, impaired barrier function, and alterations in host‒microbiome interactions. Accumulating evidence indicates that tryptophan (TRP) metabolism is associated with these core pathological processes. This review summarizes the major TRP metabolic pathways, including the kynurenine pathway, microbial indole production, and the serotonin-melatonin axis, and outlines how their respective metabolites influence cutaneous inflammation, immune regulation, and barrier integrity in the context of AD. We integrate findings from preclinical and clinical studies to describe disease-associated alterations in TRP metabolism in AD and their potential relevance to disease activity. In addition, we examine both existing and emerging therapeutic strategies aimed at correcting TRP metabolic imbalance, including pharmacological agents, dietary interventions, and probiotic supplementation. Overall, elucidating the multifaceted role of TRP metabolism in AD pathophysiology provides a rational foundation for developing more precise diagnostic tools and targeted therapeutic approaches.