Dysbiosis in the Pathogenesis of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation. Recent research highlights cutaneous dysbiosis as a critical factor in its pathogenesis. In this review, we summarize the interplay between the skin microbiota and host immunity, contrasting the homeostatic state with the dysbiosis in AD. In healthy skin, resident microbial communities, including coagulase-negative staphylococci and Cutibacterium acnes, contribute to immune education and pathogen defense. In AD, this equilibrium is disrupted, leading to a state of functional dysbiosis characterized not only by reduced microbial diversity and the predominance of Staphylococcus aureus but also by the loss of protective commensal functions. The virulence of S. aureus is pivotal, with its accessory gene regulator (Agr) quorum-sensing system driving the expression of toxins like δ-toxin, which exacerbates type 2 inflammation and barrier defects. Crucially, colonization in early life with S. aureus strains possessing a functional Agr system is strongly associated with an increased risk of subsequent AD development. This understanding has prompted a paradigm shift in therapeutic strategies. Recognizing the limitations of traditional broad-spectrum antimicrobials, which can worsen dysbiosis, novel approaches now focus on restoring microbial balance. These include bacteriotherapy using beneficial commensal strains to competitively inhibit S. aureus, quorum-quenching agents, and preventive skincare interventions initiated in infancy to foster a healthy microbiome. A deeper comprehension of these host-microbe and microbe-microbe interactions is essential for optimizing these promising microbiome-targeted therapies for AD.