Phytic Acid Improves the Skin Barrier Function in Murine Models of Atopic Dermatitis Through Skin Microbiota‐Derived Indole‐3‐Propionic Acid

ABSTRACT Background Barrier dysfunction and dysbiosis of the skin microbiota are two of the key factors in the pathogenesis of atopic dermatitis (AD). Phytic acid (PA) is a common constituent of high‐fiber foods, whereas its role in AD remains unelucidated. The aim of this study was to investigate the effects of PA‐altered skin microbial metabolites on AD and to explore its specific mechanism. Methods MC903‐induced AD mouse models were used to explore the role of PA on AD by TEWL, immunofluorescence, and qPCR analysis. Using cohouse experiments with feces removal to verify the role of skin microbiota. The specific mechanism of effect of PA was explored through 16S, RNA‐seq, LC–MS/MS, luciferase assay, and in vivo experiments with siRNA. Results Diet‐derived PA significantly improved the barrier function of MC903‐induced AD, whether administered by gavage or topically. Topical application of PA reshaped the skin microbiota in AD mice and increased tryptophan‐metabolizing bacteria, especially Staphylococcus epidermidis . Furthermore, PA upregulated skin microbiota‐derived indole derivatives, especially indole‐3‐propionic acid (IPA), thus activating AHR to promote the transcription of KRT10, which further ameliorated AD . Conclusion Our findings showed that diet‐derived PA improved barrier function in AD via altering skin microbiota‐derived metabolites, highlighting PA as a novel therapeutic strategy for the treatment of AD.