The epidermis forms a barrier that defends the body from desiccation and entry of harmful substances, while also sensing and integrating environmental signals. The tightly orchestrated cellular changes needed for the formation and maintenance of this epidermal barrier occur in the context of the skin microbiome. Using germ-free mice, we demonstrate the microbiota is necessary for proper differentiation and repair of the epidermal barrier. These effects are mediated by microbiota signaling through the aryl hydrocarbon receptor (AHR) in keratinocytes, a xenobiotic receptor also implicated in epidermal differentiation. Mice lacking keratinocyte AHR are more susceptible to barrier damage and infection, during steady-state and epicutaneous sensitization. Colonization with a defined consortium of human skin isolates restored barrier competence in an AHR-dependent manner. We reveal a fundamental mechanism whereby the microbiota regulates skin barrier formation and repair, which has far-reaching implications for the numerous skin disorders characterized by epidermal barrier dysfunction.

表皮形成一道屏障，保护身体免受干燥和有害物质的侵入，同时还能感知和整合环境信号。形成和维持这种表皮屏障所需的紧密协调的细胞变化发生在皮肤微生物组的背景下。使用无菌小鼠，我们证明微生物群对于正确分化和修复表皮屏障是必要的。这些作用是由微生物群通过角质形成细胞中的芳烃受体 (AHR) 信号传导介导的，AHR 是一种外源性受体，也与表皮分化有关。在稳态和表皮致敏期间，缺乏角质形成细胞 AHR 的小鼠更容易受到屏障损伤和感染。用特定的人类皮肤分离菌群定殖以依赖 AHR 的方式恢复屏障能力。我们揭示了微生物群调节皮肤屏障形成和修复的基本机制，这对以表皮屏障功能障碍为特征的众多皮肤疾病具有深远的影响。