LAUSR

BACKGROUND Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritus and eczema lesions and psychiatric comorbidities. The Gut-brain-skin axis plays a pivotal role during AD development, which could might be a novel therapeutic strategy for AD. Herein, the present study aims to uncover the protective effects and underlying mechanisms of fructo-oligofructose (FOS), a type of prebiotic, on AD-like skin manifestations and the comorbid anxiety and depression in AD mice. RESULTS Female Kunming mice were topically treated with 2, 4-dinitrofluorobenzene (DNFB) to induce AD-like symptoms and orally administrated with FOS daily for 14 days. The results showed that FOS could markedly alleviate AD-like skin lesions as evidenced by a dramatic decrease in severity score, scratching bouts, IgE and Th1/Th2-related cytokine levels, and the infiltration of inflammatory cells and mast cells to the dermal tissues. The comorbid anxiety and depressive-like behaviors estimated by FST, TST, OFT and ZMT in AD mice were further significantly attenuated by FOS. Importantly, FOS significantly upregulated brain neurotransmitters levels of 5-hydroxytryptamine (5-HT) and dopamine (DA). Furthermore, FOS treatment increased the relative abundance of gut microbiota, such as Prevotella and Lactobacillus and the concentrations of SCFAs, especially acetate and iso-butyrate in feces of AD mice. The correlation analysis indicated that the reshaped gut microbiome composition and enhanced SCFAs formation are associated with skin inflammation and behavioral alteration. CONCLUSION Collectively, these data identify FOS as a promising microbiota-targeted treatment for AD-like skin inflammation and the comorbid anxiety and depressive-like behaviors. This article is protected by copyright. All rights reserved.