Microbially-competent skin organotypics reveal dysregulated AhR signalling in microbial dysbiosis

Microbial dysbiosis is increasingly linked to skin disorders, yet the mechanisms driving these pathological processes remain poorly understood. This study developed microbially competent 3D skin organotypics (OTs) representing healthy (5M) and dandruff (5MP) microbiomes, to investigate host-microbial interactions. OTs colonised with 5M microbiota exhibited healthy skin morphology, while 5MP colonised OTs displayed dandruff-like phenotypes, including altered epidermal morphology, reduced barrier protein expression, and dysregulated corneodesmosome hydrolysis. Transcriptomic and protein analysis revealed attenuation of the aryl hydrocarbon receptor (AhR) signalling pathway in 5MP colonised OTs, a finding subsequently validated at the protein level in participants with dandruff. These results strongly suggest that microbial dysbiosis contributes to dandruff pathogenesis through disruption of AhR signalling, a pathway crucial for maintaining epidermal barrier function and immune homeostasis. This in vitro model provides new insights into the role of microbial dysbiosis in skin disorders and could open new avenues for host-microbiome therapeutic interventions.