Long term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-β enriched formula after weaning

Abstract

Background

Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence.

Objectives

We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it.

Methods

We quantified ovalbumin (OVA) and OVA specific immunoglobulins levels by ELISA in milk from the EDEN birth cohort. Since OVA specific Ig were found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhea in their 6 and 13-week-old progeny. In some experiments, a TGF-β enriched formula was given after weaning.

Results

At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhea after 6 and 7 OVA challenges versus 44% and 72% in mice breastfed by naïve mothers (p=0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA specific IgE (p<0.0001). At 13 weeks, although OVA specific IgE remained low (p=0.001), diarrhea occurrence increased to 32% and 46% after 6 and 7 OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-β after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared to mice breastfed by naive mothers (0%, 13% and 32% of diarrhea at the 5th, 6th and 7th challenges versus 17, 42 and 78%; p=0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared to control mice (p=0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier.

Conclusions

In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-β supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.

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