Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Abstract

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured.

Allergen Immunization Induces Major Changes in Microbiota Composition and Short-Chain Fatty Acid Production in Different Gut Segments in a Mouse Model of Lupine Food Allergy

“…Allergies have been associated with altered diversity and composition of gut microbiota [2-4, 8], and we hypothesize that effects by adjuvants on the microbiota composition are one of their mode of action. In the present model we used CT, a commonly used adjuvant in animal studies of food allergy [24], serving as a model adjuvant, since oral exposure to the allergen alone does not induce food allergy. Increased knowledge on the mechanisms on how adjuvants, including model allergens like CT, contribute to allergy development may open avenues for the identification of compounds (relevant for human exposure) with similar mechanisms of action.…”

“…Several mouse models of food allergy have been established for research purposes, and the various parameters influencing the character and intensity of the allergy endpoints are reviewed in Bøgh et al [24]. However, in spite of the use of inbred mice, standardized maintenance, handling, and exposure to the animals in the same groups, there is a considerable inter-individual variation in immune responses.…”

Food allergy in EAACI journals (2016)

“…The introduction of new protein sources into the diet may create new food allergies that, if possible, should be predicted. Robust and reliable animal models would be valuable tools for safety assessment, but, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods . Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice …”

Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

“…A variety of in vitro and in vivo models have been developed that address the factors and mechanisms involved in the sensitization to food proteins . Currently, approaches are being developed using protein chemistry and in vitro and in silico methods to characterize food proteins and derivatives that arise during product processing and reformulation, which may explain why certain food proteins induce sensitization of the immune system, while others are tolerated . However, elucidating the mechanisms underlying allergen sensitization is a complex, multidimensional problem that often requires a wide range of additional in vivo and ex vivo experimentation, as a wide range of molecules, tissues, and cells play a role in the mechanisms underlying food allergen sensitization .…”