Abstract: Objective: This study aimed to investigate the association of atopic dermatitis (AD) and anxiety/depression behaviors induced by AD with the intestinal microbiota. Additionally, it sought to evaluate the therapeutic potential of mannan oligosaccharide (MOS) in alleviating AD symptoms through the modulation of the gut microbiota and the enhancement of short-chain fatty acids (SCFAs) production. Methods: Female Kunming mice were challenged with 2,4-dinitrofluorobenzene (DNFB) to induce AD-like symptoms. MOS was administered orally daily for 14 days. On the 6th and 11th days post-modeling, the number of scratching bouts in mice was recorded. Following dissection, epidermal thickness, mast cell infiltration, and serum levels of inflammatory cytokines were measured. Meanwhile, cerebral levels of neurotransmitters, including 5-hydroxytryptamine (5-HT) and norepinephrine (NE), were assessed. The abundance of intestinal microbiota and fecal concentrations of SCFAs were also analyzed. Results: MOS significantly reduced AD-like symptoms by reducing inflammatory cytokines, as reflected in a significant decrease in the number of scratching bouts, epidermal thickness, mast cells and inflammatory cytokine levels. MOS intervention up-regulated the expression of 5-HT and NE, and consequently alleviated anxiety and depression-like behaviors. Furthermore, compared with the AD group, MOS intervention increased the gut microbiota abundance of mice, especially beneficial bacteria such as Bifidobacterium, Lactobacillus and Klebsiella. At the same time, these beneficial bacteria significantly increased the fecal contents of SCFAs, especially propionic acid. Correlation analysis indicated that AD amelioration was positively correlated with fecal SCFAs levels and the proliferation of certain intestinal microbes. Conclusion: MOS intervention could offer a novel approach to managing AD and its psychological comorbidities.

Key words: mannan oligosaccharides, atopic dermatitis, anxiety and depression-like behaviors, gut microbiota