Raw data for manuscript "Engineering microbial symbiosis and dysbiosis reveals a critical role for the AhR in scalp skin"

AbstractBackgroundDespite increasing recognition of the microbiome’s pivotal influence on skin health, the molecular mechanisms by which microbial dysbiosis drives dermatological disease remain poorly defined. A critical gap persists in understanding how shifts in the scalp microbiome drive pathological changes in epidermal architecture and immune regulation.ResultsHere, we introduce microbially competent 3D skin organotypic (OT) models, incorporating bacteria and fungi, engineered to recapitulate both healthy (5M) and dandruff (5MP) microbiomes, to investigate host-microbiome interactions. OTs colonised with 5M maintained normal epidermal morphology, whereas 5MP-colonised OTs developed dandruff-like phenotypes, including altered epidermal morphology, reduced expression of key barrier proteins, and dysregulated corneodesmosome hydrolysis. Transcriptomic analysis and protein validation revealed significant attenuation of the aryl hydrocarbon receptor (AhR) signalling pathway in 5MP colonised OTs, a finding subsequently validated in scalp samples from individuals with dandruff.ConclusionsThese results provide mechanistic evidence that microbial dysbiosis can disrupt AhR signalling, compromising epidermal barrier integrity and immune homeostasis. This in vitro model provides a versatile and clinically relevant platform for advancing our understanding of microbiome-driven skin pathology and translating mechanistic insights into precision interventions.