3′-Sialyllactose (3′-SL), a natural prebiotic, maintains immune homeostasis and exerts antiinflammatory and anti-arthritic effects. Although regulatory T cells (Tregs) prevent excessive inflammation and maintain immune tolerance, the effect of 3′-SL on Treg regulation is unclear. This study aimed to investigate the effect of 3′-SL on Treg responses in atopic dermatitis (AD) pathogenesis. Oral administration of 3′-SL reduced AD-like symptoms such as ear, epidermal, and dermal thickness in repeated topical application of house dust mites (HDM) and 2,4-dinitrochlorobenzene (DNCB). 3′-SL inhibited IgE, IL-1β, IL-6, and TNF-α secretion and markedly downregulated AD-related cytokines including IL-4, IL-5, IL-6, IL-13, IL-17, IFN-γ, TNF-α, and Tslp through regulation of NF-κB in ear tissue. Additionally, in vitro assessment of Treg differentiation revealed that 3′-SL directly induced TGF-βmediated Treg differentiation. Furthermore, 3′-SL administration also ameliorated sensitization and elicitation of AD pathogenesis by suppressing mast cell infiltration and production of IgE and proinflammatory cytokines in mouse serum by mediating the Treg response. Furthermore, Bifidobacterium population was also increased by 3′-SL administration as prebiotics. Our data collectively show that 3′-SL has therapeutic effects against AD progression by inducing Treg differentiation, downregulating AD-related cytokines, and increasing the Bifidobacterium population. Prebiotics are substances that improve the intestinal environment as a nutrient source for probiotics that help the growth of intestinal microbiota 1. Prebiotics are often composed of carbohydrates such as oligosaccharides, most of which are in the form of dietary fibre 2. Probiotics have a beneficial effect on the intestinal environment, prevent the growth of harmful bacteria in the intestine, improve immunity, ameliorate skin diseases such as atopic dermatitis (AD) and psoriasis, and inhibit metabolic syndrome 3. There are hundreds of beneficial bacteria that live in the intestine, but very few strains can be cultured outside the gut. Therefore, the only way to increase the number of desired strains without external supplementation is to use prebiotics. Notably, these beneficial microbiotas are known to be closely related to many autoimmune diseases such as AD.
