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

AbstractBackground
Despite 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.
Results
Here, 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.
Conclusions
These 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.

### 研究背景
尽管学界日益认识到微生物组（microbiome）对皮肤健康的关键调控作用，但微生物群失调驱动皮肤病发生的分子机制仍有待阐明。目前学界对头皮微生物组失衡如何引发表皮结构与免疫调控的病理性改变，仍存在显著认知空白。

### 研究结果
本研究构建了具备微生物定植能力的三维皮肤类器官（organotypic, OT）模型，整合细菌与真菌组分，用以模拟健康状态（5M）与头皮屑状态（5MP）的头皮微生物组，以此探究宿主-微生物组互作机制。定植5M微生物组的OT模型可维持正常表皮形态；而定植5MP微生物组的OT模型则出现头皮屑样表型，具体包括表皮形态异常、关键屏障蛋白表达下调以及角质桥粒水解失调。转录组分析与蛋白验证实验显示，定植5MP微生物组的OT模型中芳基烃受体（aryl hydrocarbon receptor, AhR）信号通路显著减弱，该发现随后在头皮屑患者的头皮样本中得到验证。

### 研究结论
本研究结果为微生物群失调可通过干扰AhR信号通路，进而损害表皮屏障完整性与免疫稳态提供了机制层面的直接证据。该体外模型可为深化我们对微生物组驱动的皮肤病理的理解提供多功能且具有临床相关性的研究平台，并可将机制研究成果转化为精准干预手段。