Abstract
The skin microbiome plays a vital role in maintaining skin homeostasis by regulating immune responses, preserving barrier integrity, and inhibiting pathogen colonization. This review systematically explores the mechanisms underlying its dysregulation in conditions such as acne, atopic dermatitis, psoriasis, and impaired wound healing, with a focus on key factors including microbial over colonization, diminished diversity, and host immune dysregulation. The influence of microbial metabolites, such as short-chain fatty acids and porphyrins, is also examined. We further evaluate emerging microbial-targeted therapeutic strategies, including live biotherapeutic products, skin microbiota transplantation, epigenetic and metabolic interventions, and precision antimicrobial polymers. These approaches aim to restore microbial balance rather than achieve broad-spectrum sterilization, representing a significant shift in the treatment paradigm for cutaneous diseases. In contrast to previous reviews, this article places special emphasis on the mechanisms of multi-organ interactions within the gut-skin axis and discusses the potential of integrating multi-omics technologies and artificial intelligence to advance the clinical translation of personalized microbial therapies, thereby providing a forward-looking perspective on the field.