The Dysbiosis–Barrier–Immune Axis: Unraveling the Immune Consequences of Skin Microbial Imbalance

Abstract

The skin microbiota has been reframed as a dynamic and active regulator of cutaneous barrier integrity and immune programming, moving beyond its traditional view as a passive microbial community. Dysbiosis represents a complex functional and ecological imbalance that disrupts barrier integrity and may promote sustained inflammatory immune remodeling. This mechanistic axis, in which disruption of the microbiota contributes to barrier failure and immune dysregulation, underpins chronic inflammatory skin conditions. Conventional antibiotic-centered therapies often fail to restore microbial homeostasis or immune balance, highlighting their limitations. Emerging precision microbiome therapeutics focus on targeted modulation of microbial function, signaling pathways, and ecological restoration to repair barrier defects and recalibrate immune responses. This review synthesizes current evidence linking skin microbiota dysbiosis with barrier dysfunction, inflammatory immune remodeling, and emerging microbiome-directed therapeutic strategies. We propose an integrative framework linking ecological disruption, epithelial barrier injury, and immune dysregulation while highlighting unresolved mechanistic, translational, and knowledge gaps, such as detailed molecular mechanisms of host-microbiota interactions and challenges in translating findings into clinically effective personalized interventions. Future research should prioritize multi-omics integration and biomarker-driven stratification to advance precision dermatology therapeutics grounded in mechanistic insights of skin microbial ecology.