Critical features of an in vitro intestinal absorption model to study the first key aspects underlying food allergen sensitization

Abstract

New types of protein sources will enter our diet in a near future, reinforcing the need for a straightforward in vitro (cell‐based) screening model to test and predict the safety of these novel proteins, in particular their potential risk for de novo allergic sensitization. The Adverse Outcome Pathway (AOP) for allergen sensitization describes the current knowledge of key events underlying the complex cellular interactions that proceed allergic food sensitization. Currently, there is no consensus on the in vitro model to study the intestinal translocation of proteins as well as the epithelial activation, which comprise the first molecular initiation events (ME1‐3) and the first key event of the AOP, respectively. As members of INFOGEST, we have highlighted several critical features that should be considered for any proposed in vitro model to study epithelial protein transport in the context of allergic sensitization. In addition, we defined which intestinal cell types are indispensable in a consensus model of the first steps of the AOP, and which cell types are optional or desired when there is the possibility to create a more complex cell model. A model of these first key aspects of the AOP can be used to study the gut epithelial translocation behavior of known hypo‐ and hyperallergens, juxtaposed to the transport behavior of novel proteins as a first screen for risk management of dietary proteins. Indeed, this disquisition forms a basis for the development of a future consensus model of the allergic sensitization cascade, comprising also the other key events (KE2‐5).

Cytotoxicity and Bioimmunological Activity of Poly(2-Isopropenyl-2-oxazoline) Conjugates with Ibuprofen Using 3D Reconstructed Tissue Models

“…The study of Payen et al aimed to analyze the effect of IL-6 on EpiIntestinal, a 3D human small intestinal tissue model with epithelial polarity, allowing good evaluation of metabolism and drug transport in this tissue model . The EpiIntestinal tissue model was also suggested as an in vitro model for testing intestinal allergen translocation and epithelial translocation …”

Research gaps and future needs for allergen prediction in food safety

“…There are an assortment of additional human cell and tissue models that might potentially be relevant for an allergenicity risk assessment such as biopsy-based models, coculture systems with epithelial and immune cells, precision cut organ slices, organoids, e.g., mini-gut cultures and organ-on-a chip models (gut-on-chip) ( 39 – 41 ). Moreover, there are in vitro models evaluating the potential sensitising capacity of food proteins such as antigen uptake via the intestinal mucosal barrier ( 42 , 43 ). However, some of these models might need considerable work to ensure predictability and cost-effectiveness.…”

Allergenic Shrimp Tropomyosin Distinguishes from a Non-Allergenic Chicken Homolog by Pronounced Intestinal Barrier Disruption and Downstream Th2 Responses in Epithelial and Dendritic Cell (Co)Culture

“…Most food allergic reactions are induced by peanut-, cow’s milk-, egg-, soy-, wheat-, tree nut-, fish-, and shellfish-containing products [ 2 ], but numerous other food allergens have been identified [ 3 ]. Allergenic food proteins often possess intrinsic properties to promote allergic sensitization, including intestinal epithelial activation and permeabilization [ 4 , 5 , 6 , 7 , 8 , 9 ]. This mucosal immune activation can lead to the activation of dendritic cells (DC) and subsequent polarization of a type 2 T cell response which drives the development of allergen-specific IgE production and IgE-mediated clinical reactions upon subsequent encounter with the allergen [ 10 ].…”