Atopic dermatitis: Multi-omics insights into microbiota-driven modulation of the gut-skin axis

Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease resulting from complex interactions among host genetics, immune dysregulation, and microbial imbalance. Recent advances in multi-omics technologies have revealed distinct AD endotypes characterized by specific genetic variants, microbial enterotypes, and metabolite profiles. Emerging evidence highlights the gut-skin axis as an important regulatory pathway, in which alterations in gut microbiota influence the production of key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan-derived aryl hydrocarbon receptor (AHR) ligands, thereby modulating Th2-dominant inflammatory responses. Integrated analyses combining metagenomics, metabolomics, and single-cell transcriptomics have further identified endotype-specific signatures, such as Bacteroides-enriched profiles associated with lipopolysaccharide-driven inflammation and Prevotella-dominant clusters linked to enhanced AHR activation and epithelial barrier repair. These findings provide a basis for precision stratification and the development of targeted therapeutic strategies, including genotype-guided biologics, microbiota modulation, engineered probiotics, phage therapy, and fecal microbiota transplantation. This review summarizes current evidence integrating host genetics, microbiota networks, and multi-omics biomarkers to provide a comprehensive framework for understanding AD endotypes and to highlight potential avenues for precision diagnosis and targeted interventions.