Gut Microbiome Dysbiosis in Atopic Dermatitis and Critical Illness: Pathogenic Mechanisms, Gut–Skin Axis Disruption, and Emerging Microbiota-Targeted Therapies

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease affecting more than 171 million individuals worldwide. Increasing evidence indicates that its pathogenesis extends beyond cutaneous immune dysregulation and involves systemic interactions mediated by the gut microbiome. This narrative review summarizes current knowledge regarding the gut–skin axis in AD and highlights three emerging areas of translational relevance: (i) the relationship between gut microbial dysbiosis, microbial metabolite alterations, and validated disease severity indices; (ii) the role of short-chain fatty acids (SCFAs), tryptophan-derived aryl hydrocarbon receptor (AhR) ligands, and secondary bile acids as key mediators of gut–skin immune communication; and (iii) the integration of artificial intelligence (AI) and multi-omics technologies in precision microbiome medicine. Gut dysbiosis in AD is characterized by reduced abundance of beneficial taxa, including Bifidobacterium, Faecalibacterium prausnitzii, Blautia, and Akkermansia muciniphila, resulting in impaired regulatory T-cell function, enhanced Th2 polarization, increased IgE production, and disruption of epithelial barrier homeostasis. Altered concentrations of microbial metabolites, particularly SCFAs and tryptophan-derived compounds, are associated with disease activity and correlate with clinical severity scores, including the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD). Intestinal barrier dysfunction, reflected by elevated zonulin, lipopolysaccharide-binding protein, and Reg3A, further amplifies systemic inflammation and cutaneous sensitization. Microbiome-targeted interventions—including probiotics, synbiotics, dietary modulation, and fecal microbiota transplantation (FMT)—have demonstrated promising effects on disease severity, immune regulation, and the restoration of microbial diversity. Emerging AI-driven multi-omics approaches are enabling the identification of disease endotypes, microbial signatures, and metabolite profiles with potential diagnostic, prognostic, and therapeutic value. Additionally, evidence from critical illness research suggests that ICU-associated dysbiosis may represent an extreme model of gut–skin axis disruption, providing novel insights into microbiome-driven immune dysfunction. Collectively, current evidence supports the gut microbiome as a driver, biomarker, and therapeutic target in AD. Future research should prioritize standardized multi-omics studies, metabolite-based biomarkers, and precision microbiome interventions to facilitate the translation of discoveries from the gut–skin axis into clinical practice.