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

A. Rekima, P. Macchiaverni, M. Turfkruyer, S. Holvoet, L. Dupuis, N. Baiz, I. Annesi-Maesano, A. Mercenier, S. Nutten, V. Verhasselt

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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 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. Results: 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. 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.

Original languageEnglish
Pages (from-to)565-576
Number of pages12
JournalClinical and Experimental Allergy
Issue number4
Publication statusPublished - 1 Apr 2017


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