Microbiota-directed therapies for atopic dermatitis: a three-tier framework for inflammation control, immune modulation, and microbiome restoration.

The pathogenesis of atopic dermatitis (AD) involves cutaneous barrier dysfunction, immune dysregulation, and microbiota imbalance. Although microbiota-directed therapeutic approaches have garnered increasing attention, current evidence is heterogeneous, encompassing probiotics, postbiotics, microbial metabolites, local microbial interventions, antimicrobials and ecological modulation strategies. This narrative review does not aim to provide clinical guidelines, but rather seeks to synthesise existing evidence within a three-tier conceptual framework. This framework classifies interventions into three categories: those primarily addressing local inflammation and barrier-associated microbiota dysbiosis; those exerting systemic immunomodulation via gut-derived microbial signals; and those modulating the skin microbiota ecology. It should be noted that human clinical data are still limited and heterogeneous, and much mechanistic insight is derived from preclinical research. By clarifying mechanistic layers and evidentiary gaps, this framework may facilitate future research to evaluate the sequencing or combination of anti-inflammatory therapy, barrier restoration, and microbiota ecological modulation.