A specific mixture of non-digestible oligosaccharides enhances the tolerizing capacity of a partial whey hydrolysate in a mouse model for cow's milk allergy

Abstract

Hypoallergenic infant formulas (HA) are considered a good alternative for infants at high risk for developing allergy if breastfeeding is not possible. Dietary intervention studies with HA combined with a specific mixture of non-digestible oligosaccharides, have been shown to reduce allergic symptoms in these children. However, the mechanisms by which these oligosaccharides exert their effect are yet to be explored. In this study, the contribution of this specific oligosaccharides mixture on the tolerizing capacity of a partial whey hydrolysate (WH) was investigated in a mice model of cow's milk allergy. Mice were sensitized orally with whey using cholera toxin as adjuvant. Prior to sensitization mice were pre-treated orally with partial WH, PBS, with or without supplementation with the specific oligosaccharide mixture containing short chain-galacto-, long chain-fructo- and acidic-oligosaccharides (9:1:1). After challenge, the acute allergic skin response, the mast cell mediator mMCP-1 and whey-specific antibodies were measured. The presence of Foxp3+regulatory T-cells and CD103+DC were determined in mesenteric lymph nodes. Oral pre-treatment of mice fed the partial WH induced tolerance as refl ected by a reduced acute allergic skin response and a suppressed mMCP-1 release without affecting whey-specific IgE levels. This effect coincided with increased CD103+DC and Foxp3+regulatory T-cell numbers. Interestingly, a combination of the partial WH and oligosaccharide diet completely abolished the acute allergic skin response and mMCP-1 release. In addition, a tendency towards decreased IgE levels and a further increase in intestinal CD103+DC numbers was observed. A specific mixture of non-digestible oligosaccharides enhanced the capacity of a partial WH to induce oral tolerance. This effect was associated with increased numbers of CD103+DC in the mesenteric lymph nodes, suggesting a role of these cells in the observed tolerance inducing capacity of this specific oligosaccharide mixture combined with partial WH.