Abstract: Objective: To investigate the influence of xylooligosaccharides on skin inflammation, behavioral characteristics, neurotransmitters, and gut flora in a mouse model of atopic dermatitis (AD) induced by 2,4-dinitrofluorobenzene (DNFB). Methods: The AD mouse model was created by administration of DNFB for 14 consecutive days. The scoring atopic dermatitis index, enzyme-linked immunosorbent assay (ELISA), histopathology, and immunohistochemical analyses were used to assess inflammation and depression-like behaviors. Furthermore, high-throughput 16S rRNA gene sequencing was used to determine the composition of fecal microbiota. Results: Xylooligosaccharides treatment reduced the number of scratches and skin thickness, mast cell infiltration and the levels of immunoglobulin (Ig) E and T-helper cytokines compared with the AD model group. Meanwhile, xylooligosaccharides treatment reduced the immobility time of mice in the forced swimming test and increased the total movement distance and movement distance in the center area in the open-field test. Furthermore, 5-hydroxytryptamine and dopamine expression in the brain was increased following xylooligosaccharides treatment. Using network pharmacology, gene ontology analysis showed that the targets were mainly enriched in phosphatase binding and the regulation of leukocyte differentiation, which ameliorated AD mainly through the hypoxia inducible factor-1 and phosphatidylinositide 3-kinase-protein kinase B pathways. 16S rRNA gene sequencing, diversity indices, and gut microbial taxonomic composition analysis showed DNFB-induced changes in intestinal microbiota diversity in AD mice. Comparative analysis indicated that xylooligosaccharides intake improved the gut microbiome by dramatically enhancing the concentration of Lactobacillus while decreasing the concentration of Bacteroides in mice. Conclusion: Xylooligosaccharides reduce inflammatory dermatosis and related depression-like behaviors via regulating intestinal homeostasis, having medicinal value as a nutritional and functional ingredient.

Key words: atopic dermatitis; intestinal flora; xylooligosaccharides; depression-like behaviors