Genotype-Environment-Driven Dysbiosis in the Skin Microbiome of Ichthyosis

Many factors might be expected to influence the cutaneous microbiome, especially on diseased skin. Yet, few studies account for the complex interactions between host and environmental factors. To shed light on such interactions, we characterized the skin microbiome from 7 types of ichthyosis and confirmed previous reports of genotype-related and barrier-related effects. We then focused on the TGM1 genotype and assessed the association between the microbiome features and the ichthyosis genotype and phenotype while adjusting for contextual host covariables, including clinical treatments. We showed that the ichthyosis genotype and phenotype interact-sometimes antagonistically-with treatment to influence the composition and metabolic potential of the skin microbiome at species, strain, and metabolic pathway levels. Notable interactions with the TGM1 genotype included transepidermal water loss and emollient and retinoid use. Larger groups of patients and additional measurements will be needed to unravel the complex interactions that impact host and environmental influences on skin microbiome.