title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: University of Nice Sophia Antipolis, TIM, EA 6302, Nice, France.
authors.forename: A
authors.initials: A
authors.lastname: Rekima
authors.affiliation: Institute of Biomedical Sciences - University of São Paulo, São Paulo, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Macchiaverni
authors.affiliation: University of Nice Sophia Antipolis, TIM, EA 6302, Nice, France.
authors.forename: M
authors.initials: M
authors.lastname: Turfkruyer
authors.affiliation: Nestle Research Center, Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Holvoet
authors.affiliation: Nestle Research Center, Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Dupuis
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Medical School Saint-Antoine, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Baiz
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Medical School Saint-Antoine, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Annesi-Maesano
authors.affiliation: Nestle Research Center, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Mercenier
authors.affiliation: Nestle Research Center, Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Nutten
authors.affiliation: University of Nice Sophia Antipolis, TIM, EA 6302, Nice, France.|The International Inflammation 'in-FLAME' Network, Worldwide Universities Network, Perth, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Verhasselt
mesh_terms: D000821:Animal Feed; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001942:Breast Feeding; D003967:Diarrhea / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D005512:Food Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008895:Milk, Human / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014886:Weaning
chemical_list: D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: animal models; food allergy; immunotherapy and tolerance induction; paediatrics; prevention