Prevention of cow's milk protein allergy in vivo by early exposure to betalactoglobulin-derived peptides and synbiotics

Background: Oral tolerance is a promising approach for allergy management in early life but it strongly depends on allergen exposure. Presentation of specific allergens to children at-risk of developing allergic disease can possibly be done with small allergen-derived peptides with toleranceinducing capacities. Dietary interventions, such as synbiotics (a combination of specific non-digestible oligosaccharides and beneficial bacteria), might have a promising role as an adjunct therapy for food allergy. This study aimed at investigating the efficacy of specific cow's milk protein-derived peptides together with a synbioticsenriched diet on preventing the onset of cow's milk allergy. Method: Three-week-old female C3H/ HeOuJ mice (N = 4-8) were exposed orally to PBS (control), cow's milk whey protein (max. tolerance) or to a mixture of synthetic peptides derived from beta-lactoglobulin, a main allergen in whey, while on a control or a synbiotics-enriched diet. Mice were sensitized and underwent an intradermal whey challenge after which clinical signs of allergy were recorded. Mice were challenged orally, followed by blood collection and sacrifice. Serum allergen-specific immunoglobulins, mouse mast cell protease 1 (mMCP-1) and allergen-induced cytokine production by splenocytes were measured by ELISA while T cell subsets in the spleen and small intestine lamina propria were determined by flow cytometry. Results: Pre-exposing young mice to a low dosage of peptides while feeding them a synbiotics-enriched diet, results in a significant reduction of the acute allergic skin response to whey (P <0.05) when compared to the allergic control group. Although we did not observe an effect on serum immunoglobulins and mMCP-1 levels, mice with reduced allergic skin response were associated with less severe anaphylactic symptoms (P <0.0001). Lower levels of allergen-induced cytokines by splenocytes and a restored Th1/Th2 balance (P <0.05) in the small intestine lamina propria were the hallmarks underlying the protective effect of the peptides-synbiotics intervention. Conclusion: In conclusion, the combined exposure to specific beta-lactoglobulin derived peptides in combination with a synbiotics-enriched diet may support oral tolerance induction by preventing the onset of allergic symptoms and improving the intestinal Th1/Th2 balance.