Food allergen sensitization on a chip: the gut–immune–skin axis

The global population is growing, rapidly increasing the demand for sustainable, novel, and safe food proteins with minimal risks of food allergy. In vitro testing of allergy-sensitizing capacity is predominantly based on 2D assays. However, these lack the 3D environment and crosstalk between the gut, skin, and immune cells essential for allergy prediction. Organ-on-a-chip (OoC) technologies are promising to study type 2 immune activation required for sensitization, initiated in the small intestine or skin, in interlinked systems. Increasing the mechanistic understanding and, moreover, finding new strategies to study interorgan communication is of importance to recapitulate food allergen sensitization in vitro. Here, we outline recently developed OoC platforms and discuss the features needed for reliable prediction of sensitizing allergenicity of proteins.