Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome via Cell

The skin microbiome is a fundamental component of the skin barrier, consisting of unique microbial communities distinct from those of other barrier organs. Commensal microbes on the skin enhance epithelial barrier function by regulating differentiation via the aryl hydrocarbon receptor (AHR). In this study, we developed a gnotobiotic model by colonizing germ-free (GF) mice with a synthetic microbial community comprising fifty distinct microbes isolated from healthy human skin, designed to represent the human skin microbiome. Using this ecological framework, we identified tryptophan metabolites produced by this synthetic microbiome and demonstrated their role in improving epithelial barrier function through AHR regulation. This proof-of-concept study illustrates the potential to harness host-microbiome-mediated metabolism in stratified epithelia to enhance skin barrier defenses. A comprehensive understanding of the mechanisms driving interactions within the skin ecosystem could lead to innovative, personalized, and cost-effective therapies that leverage host-microbiome interactions.