A Multilevel Perspective on the Skin: Skin Architecture, Microbial Communities, Intrinsic Metabolites, and Emerging AI-Enabled Applications

The skin is the largest organ of the human body and harbors a diverse microbial community that constitutes a complex ecosystem. Despite advances in next-generation sequencing (NGS) that have greatly facilitated the characterization of skin microbiota composition, a critical gap remains in understanding how intrinsic metabolites mediate host–microbe interactions and maintain microecological homeostasis. This review synthesizes current knowledge across interconnected layers of the skin ecosystem, including architecture, microbial communities, metabolites, and computational analytics. The skin’s structural features create spatially heterogeneous microenvironments that dictate microbial colonization patterns, while microbial communities have evolved adaptive strategies to exploit distinct metabolic niches. Intrinsic metabolites, encompassing lipids, proteins/peptides, ions, vitamins, and carbohydrates, constitute the chemical language through which host and microbes reciprocally communicate. The complexity of these interactions poses challenges for traditional analytical approaches, yet artificial intelligence is transforming the field by enabling progressive deepening of understanding, from predicting microbial functional potential to decoding the skin microbiome as a carrier of biological information. This multilevel framework provides a foundation for future investigations and may inform the development of personalized strategies for skin health management.