To assess the impact of the cutaneous immune response on the structure and composition of the skin microbiome, Oh et al. examined the skin microbiomes in patients with three rare monogenic primary immunodeficiencies (PIDs). Although these diseases have different extracutaneous clinical manifestations, they are all associated with atopic dermatitis (AD)-like eczema. Using 16S rRNA sequencing, the authors compared the bacterial microbiomes that were present at four different skin sites in 41 patients with PID with those that were present in patients with classical AD who were undergoing treatment and healthy controls. The PIDs were associated with increased permissivity to colonization and altered community diversity, along with decreased site specificity and longitudinal stability. Patients with PID often develop fungal infections, and internal transcribed spacer region 1 (ITS1) sequencing of a subset of the these patients showed an increased abundance of Aspergillus and Candida spp. compared with controls, leading the authors to suggest that the skin may function as a reservoir for recurrent fungal infections.