Omics-based decoding of molecular and metabolic crosstalk in the skin barrier ecosystem

Skin homeostasis depends on interactions between epithelial cells and the microbiome mediated by molecular and biochemical factors. Perturbations of this interplay are linked to inflammatory disorders, including wound healing and cancer. While research has mainly illuminated shifts in microbial community composition, novel computational approaches are starting to reveal the host-microbe functional interactome in the cutaneous ecosystem. In this review, we specifically focus on known molecular and metabolic mechanisms linking skin epithelial cells and microorganisms in health and disease. Additionally, we summarise computational tools available to investigate these interactions integrating omics data. Furthermore, we present potential applications of this functional crosstalk to advance therapies targeting skin pathologies. Finally, we propose a comparative interactomics approach to envision the existence of ecological memories in the skin ecosystem, in parallel with the one described in the gut, hypothesising a link between epithelial and microbial memories in barrier tissues.