Alternatives Integrating Omics Approaches for the Advancement of Human Skin Models: A Focus on Metagenomics, Metatranscriptomics, and Metaproteomics.

The human skin microbiota, a complex community of bacterial, fungal, and viral organisms, plays a crucial role in maintaining skin homeostasis and regulating host-pathogen interactions. Dysbiosis within this microbial ecosystem has been implicated in various dermatological conditions, including acne vulgaris, psoriasis, seborrheic dermatitis, and atopic dermatitis. This review, for the first time, provides recent advancements in all four layers of omic technologies-metagenomics, metatranscriptomics, metaproteomics, and metabolomics-offering comprehensive insights into microbial diversity, in the context of functional skin modeling. Thus, this review explores the application of these omic tools to in vitro skin models, providing an integrated framework for understanding the molecular mechanisms underlying skin-microbiota interactions in both healthy and pathological contexts. We highlight the importance of developing advanced in vitro skin models, including the integration of immune components and endothelial cells, to accurately replicate the cutaneous microenvironment. Moreover, we discuss the potential of these models to identify novel therapeutic targets, enabling the design of personalized treatments aimed at restoring microbial balance, reinforcing the skin barrier, and modulating inflammation. As the field progresses, the incorporation of multi-omic approaches into skin-microbiome research will be pivotal in unraveling the complex interactions between host and microbiota, ultimately advancing therapeutic strategies for skin-related diseases.