Gut Microbiota Influence Host Metabolism and Immune Responses in Atopic Dermatitis: A Next-Generation Sequencing-Based Functional Profiling Study

Purpose: Gut dysbiosis has been linked to immune imbalance in allergic diseases, but the underlying mechanisms remain unclear. We aimed to verify whether gut microbiota composition is associated with cellular, metabolic, and immune pathways in atopic dermatitis. Patients and Methods: Fifty adults with atopic dermatitis and 25 sex- and age-matched healthy controls were enrolled. Gut microbiome composition was assessed using V3–V4 16S rRNA sequencing. Functional pathways were inferred from microbiome data using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States). Results: Despite only subtle differences in microbiota composition between patients with atopic dermatitis and controls, PICRUSt analysis identified significant differences in 149 functional pathways. Key pathways enriched in atopic dermatitis involved signal transduction mediated by protein kinases, as well as carbohydrate and lipid metabolism. Downregulated pathways included those related to energy metabolism, amino acid and nucleotide metabolism, antigen processing, and innate immune responses. In patients with atopic dermatitis, microbial diversity increased with EASI scores and IgE levels, correlating with additional predicted functional shifts. Conclusion: Our results suggest that even subtle structural differences in gut microbiota may exert significant functional effects in atopic dermatitis. Altered pathways could contribute to immune imbalance and impaired epidermal barrier function. These findings underscore the importance of incorporating functional analyses into future gut microbiota studies of atopic dermatitis to help identify therapeutic targets, including candidate probiotic strains for supplementation. Plain Language Summary: Bacteria living in the gut, known as the gut microbiome, may play a role in the development of certain diseases. Changes in the diversity and composition of the gut microbiome have been linked to atopic dermatitis, a skin condition that causes itchy lesions and greatly affects quality of life. However, few studies have examined how gut bacteria may influence metabolism and immune responses in people with atopic dermatitis. In our study, we analyzed the gut microbiome of 50 adults with atopic dermatitis and 25 healthy individuals using sequencing methods and a software tool called PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States). Despite only subtle differences of microbiome composition between the groups, PICRUSt predicted changes in many metabolic, cellular, and immune-related pathways. These included carbohydrate, lipid, and amino acid metabolism, innate immune responses, and signal transduction pathways that may contribute to inflammation and skin barrier problems seen in atopic dermatitis. Our findings suggest that even when overall microbiome diversity appears similar, subtle changes in gut bacteria may still have important effects on metabolism and immune function. Future studies should combine microbiome and metabolic analyses to confirm these results and may help guide targeted treatments, such as probiotic supplementation. Keywords: atopic dermatitis, gut microbiome, immunity, metabolism, microbiota