3′-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models

Abstract

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.

Role of Short Chain Fatty Acids and Apolipoproteins in the Regulation of Eosinophilia-Associated Diseases

“…During the last decade, several studies pointed out the beneficial and anti-inflammatory effects of a high-fiber diet and prebiotics such as poly- and oligosaccharides in murine models of atopic dermatitis [ 164 , 165 , 166 , 167 ]. Besides dietary fibers, the impact of probiotic supplementations on experimental atopic dermatitis was intensively studied, revealing a changed gut microbiota and the associated increase in SCFAs as a possible therapeutic mechanism [ 168 , 169 , 170 , 171 ].…”

The Human Milk Oligosaccharide 3’Sialyllactose Promotes Inflammation Resolution and Reduces Atherosclerosis Development in Mice

“…Importantly, we show that the anti-inflammatory effects of 3’SL in vitro translated in attenuated atherosclerosis lesion development in vivo . Anti-inflammatory effects of 3’SL in vivo were previously shown in mouse models of rheumatoid arthritis and atopic dermatitis 40, 81 . However, the authors administered 3’SL orally and thus it cannot be excluded that the anti-inflammatory phenotypes are due to likely drastic changes in the gut microbiome 34, 81 .…”

Therapeutic Single Compounds for Osteoarthritis Treatment

“…Administration of 3′-sialyllactose reduced ear, epidermal, and dermal thickness in a mouse model of atopic dermatitis, downregulated the expression of pro-inflammatory and atopic dermatitis-related cytokines, and suppressed mast cell infiltration and IgE levels. Further, 3′-sialyllactose induced transforming growth factor-β-mediated Treg differentiation in an in vitro system [ 103 ]. Experiments in both in vitro and ex vivo systems showed that 3′-sialyllactose restored IL-1β-induced reduction of COL2A1 expression as well as promoted the accumulation of sulfated proteoglycan, which is a critical factor for cartilage regeneration in OA development [ 104 ].…”