Microbiome dysbiosis and therapeutic restoration in atopic dermatitis

Atopic dermatitis (AD) is increasingly recognized as a chronic inflammatory skin disease driven by a self-reinforcing vicious cycle involving skin barrier dysfunction, immune dysregulation, and cutaneous microbiome dysbiosis. A hallmark of this dysbiosis is the overrepresentation of pathogens like <i>Staphylococcus aureus</i> and <i>Malassezia</i> species, alongside a marked loss of microbial diversity, particularly during disease flares. This review systematically dissects the host-derived factors-such as altered lipid profiles, reduced antimicrobial peptides, and elevated skin pH-that facilitate <i>S. aureus</i> colonization. We further examine how bacterial virulence factors amplify type 2 inflammation and impair barrier integrity, thereby sustaining the pathological loop. We also explore the emerging roles of the skin virome, particularly the phageome, and discuss how microbiome-targeted interventions, including bacteriotherapy with commensal bacteria and precision phage therapy, offer promising avenues for ecological restoration. Finally, we argue that future research must leverage multi-omics to understand strain-specific functions, ultimately guiding the development of personalized microbiome interventions for AD.