Combined exposure to betalactoglobulin-derived tolerogenic peptides and synbiotics alleviates food allergy response in vivo

Background: At-risk infants can be prevented from developing food allergy symptoms by feeding them hypoallergenic formulas containing cow's milk protein hydrolysates. This preventive effect might be a result of oral tolerance induction by immunogenic peptide fractions in the hydrolysates. Early exposure to toleranceinducing peptides could prevent the development of allergic symptoms. It is hypothesised that synbiotics (pre- and probiotics) can further enhance tolerance induction. Method: Three-week-old female C3H/ HeOuJ mice (N = 6-8) were exposed orally to (1) PBS (positive control for allergy), to (2) whey protein (positive control for tolerance induction), or (3) a low dose mixture of beta-lactoglobulin-derived peptides (18 amino acids) with a synbiotics-enriched diet prior to sensitization. Thereafter, the mice were fed a control cow's milk protein-free diet and sensitized to whey protein using cholera toxin as an adjuvant. Mice were intradermally challenged with whey protein, and clinical symptoms, such as acute allergic skin response and anaphylactic shock, were measured. Results: The combination of the peptide intervention with a synbiotics-enriched diet resulted in a significant reduction in the acute allergic skin response compared to the allergic positive control. Furthermore, the combined peptides-synbiotics exposure prevented from developing significantly higher anaphylactic shock symptoms when compared to the sham-sensitized controls. Conclusion: Oral exposure to specific betalactoglobulin- derived peptides with synbiotics leads to protection against acute allergic responses. The beta-lactoglobulinderived peptides were administered at a dosage 100-fold lower than previously described by Meulenbroek et al. [1], therefore a combined approach like this might reduce the peptide dose needed to prevent allergy. Future research is needed for unravelling the underlying mechanisms of the preventive effect of this combined exposure.