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.

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.

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

At 6 weeks, only 13% and 34% of mice breastfed by OVA‐exposed mothers exhibited diarrhoea after six and seven OVA challenges vs. 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), diarrhoea occurrence increased to 32% and 46% after six and seven 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 with mice breastfed by naive mothers (0%, 13% and 32% of diarrhoea at the fifth, sixth and seventh challenges vs. 17, 42 and 78%; P = 0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared with control mice (P = 0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier.

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.