title: Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy.
abstract: BACKGROUND
  Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur.
  
  
  OBJECTIVE
  We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives.
  
  
  METHODS
  We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea.
  
  
  RESULTS
  Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen-presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25hiregulatory T cells among CD4+T cells in the mesenteric lymph nodes.
  
  
  CONCLUSIONS
  A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies.
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: H
authors.identifier: http://orcid.org/0000-0001-7028-7308
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsuhara
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miotani
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sako
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.|Department of Pediatrics, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015415:Biomarkers; D002633:Chemotaxis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005503:Food Additives / Q000008:administration & dosage / Q000009:adverse effects*; D005512:Food Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D012439:Saccharin / Q000008:administration & dosage / Q000009:adverse effects; D013549:Sweetening Agents / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000485:Allergens; D015415:Biomarkers; D005503:Food Additives; D007074:Immunoglobulin G; D013549:Sweetening Agents; D007073:Immunoglobulin E; D010047:Ovalbumin; D012439:Saccharin
keywords: anaphylaxis; animal models; food additives; food allergy; oral tolerance; ovalbumin