Gut dysbiosis and microbial metabolites in atopic dermatitis: implications for immune regulation along gut-skin axis

Atopic dermatitis (AD) is a multifactorial skin disorder characterized by immune dysregulation, impaired epidermal barrier, and strong microbial imbalance. Although genetic susceptibility and environmental triggers are established AD drivers, growing evidence highlights the gut skin axis as an important but underexplored AD pathogenesis factor. Gut microbiota dysbiosis, loss of short-chain fatty acid (SCFA)-producing bacteria, and altered metabolite profiles, such as tryptophan derivatives and secondary bile acids, have been linked to systemic immune imbalance and skin inflammation. However, the precise mechanism by which gut microbial alterations influence cutaneous immunity remains unclear. This review synthesizes recent advances from clinical and experimental studies to delineate how the gut microbiota and their metabolites shape the immune response, regulate the integrity of the epithelial barrier, and modulate AD severity. By integrating emerging insights into early-life microbial colonization, metabolite-mediated immune programming, and therapeutic interventions, including prebiotics, probiotics, and microbial-derived metabolites, the current gaps and the translational potential of targeting the gut- skin axis. The knowledge consolidated here advances our understanding of AD beyond skin-focused perspectives and highlights new avenues for microbiome-based preventive and therapeutic strategies.