Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy

Clin Exp Allergy. 2017 Sep;47(9):1204-1213. doi: 10.1111/cea.12928. Epub 2017 May 8.


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 CD25hi regulatory T cells among CD4+ T cells in the mesenteric lymph nodes.

Conclusions and clinical relevance: 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.

Keywords: anaphylaxis; animal models; food additives; food allergy; oral tolerance; ovalbumin.

MeSH terms

  • Administration, Oral
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Animals
  • Antigen-Presenting Cells / immunology
  • Biomarkers
  • Chemotaxis / immunology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Food Additives / administration & dosage
  • Food Additives / adverse effects*
  • Food Hypersensitivity / immunology*
  • Immune Tolerance*
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Mice
  • Ovalbumin / immunology
  • Saccharin / administration & dosage
  • Saccharin / adverse effects
  • Sweetening Agents / administration & dosage
  • Sweetening Agents / adverse effects*


  • Allergens
  • Biomarkers
  • Food Additives
  • Immunoglobulin G
  • Sweetening Agents
  • Immunoglobulin E
  • Ovalbumin
  • Saccharin