Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we characterized skin microbial communities coupled to the global pattern of cutaneous gene expression. Patients with atopic dermatitis (AD, n=82) or psoriasis (PSO, n=119) lesions were recruited to the study and sampled for the skin microbiota and skin transcriptome. The skin microbiota was analysed by 16S rRNA gene  and whole genome sequencing, and the skin transcriptome by DNA microarrays, followed by exploratory analysis and integration of the data layers. Atopic dermatitis and psoriasis were classified by distinct microbes, which differed from healthy volunteer (HV, n=115) microbiome composition and relative abundance. The AD associated bacterial community was dominated by a single microbe (S. aureus), functionally enriched for bacterial toxins, the two-component system and glycolysis, and associated with a disease relevant host transcriptomic signature enriched for modulation of the epithelial barrier, tryptophan metabolism and immune activation. In contrast, PSO was characterized by co-occurring communities of microbes with weak associations with disease relevant gene expression. Our work underscores the importance of distinct microbial classes in tissue inflammation and provides a basis for discovery of biomarkers and targeted therapies in skin dysbiosis.

Host-microbial dialogues in atopic dermatitis and psoriasis