Unraveling the Complexity of the Skin Microbiome: Advancing Research Through Optimal Biological Models

The human skin microbiome, a complex ecosystem of diverse bacteria, plays vital roles in skin health and immunity through interactions with the host. Understanding these dynamics is crucial for advancing skin microbiome knowledge and its implications for human health. An appropriate biological model choice is pivotal for effective experimental studies. While various systems like 3D models, microfluidic coculturing, and ex vivo tissue culture have been proposed, the laboratory mouse remains the preferred model in skin microbiome research due to advantages like genetic manipulability, cost-effectiveness, and ease of handling. Moreover, mouse inner ear skin resembles human skin in shape and microbiota composition. Extensive mouse model research has illuminated the skin barrier’s structure, skin microbiota–immune system interactions, and the effects of factors like environmental exposures and genetic mutations on microbiome composition and diversity. Specific bacterial species’ roles in skin health and disease, including their impact on immune responses and skin homeostasis, have been elucidated. Mouse models have also shown the potential of certain bacterial strains to reduce skin inflammation, hinting at microbiome-targeted therapies. 3D models, microfluidic coculturing, and ex vivo tissue culture offer unique advantages for studying host–microbe interactions and tissue physiology. Integrating these systems with traditional mouse models provides a holistic approach to explore the complex dynamics of the skin microbiome’s impact on human health.