Dietary Tryptophan Restriction Remodels the Skin Metabolic Environment and Drives Microbial Community Restructuring

Tryptophan (Trp) is an essential amino acid that links metabolism, immunity, and barrier tissue homeostasis, and plays a central role in host-microbiota interactions. However, how systemic Trp availability shapes skin biology remains incompletely understood. Here, we investigated the impact of dietary Trp depletion on skin homeostasis. Using a controlled Trp-restriction model, we show that reduced Trp availability broadly alters cutaneous Trp metabolism at the host-microbial interface, with modulation of the kynurenine, serotonin, and indole pathways. These changes were associated with selective dysregulation of aryl hydrocarbon receptor (AhR) signaling in the skin, without affecting immune cell composition at steady state. Dietary Trp deficiency also induced early and significant alterations in the skin microbiota, characterized by reduced diversity and shifts in community structure, including the expansion of specific bacterial taxa. In contrast, microbiota changes in the gut were more limited, indicating a tissue-specific response to systemic Trp availability. Together, our findings identify dietary Trp as a key regulator of skin metabolic and microbial homeostasis, highlighting coordinated interactions between host pathways and the skin microbiota.