Intestinal protein uptake and IgE-mediated food allergy

[Display omitted] •Dietary proteins may cross the epithelial layer by various routes of uptake.•The faith of proteins during intestinal uptake depends on the exact mechanisms involved.•In allergic individuals, allergens may cross the epithelial layer by unique mechanisms.•Various intrinsic and extrinsic factors affect protein uptake, yet knowledge is limited.•More knowledge on how mechanisms of protein uptake affects development of food allergy is needed. Food allergy is affecting 5–8% of young children and 2–4% of adults and seems to be increasing in prevalence. The cause of the increase in food allergy is largely unknown but proposed to be influenced by both environmental and lifestyle factors. Changes in intestinal barrier functions and increased uptake of dietary proteins have been suggested to have a great impact on food allergy. In this review, we aim to give an overview of the gastrointestinal digestion and intestinal barrier function and provide a more detailed description of intestinal protein uptake, including the various routes of epithelial transport, how it may be affected by both intrinsic and extrinsic factors, and the relation to food allergy. Further, we give an overview of in vitro, ex vivo and in vivo techniques available for evaluation of intestinal protein uptake and gut permeability in general. Proteins are digested by gastric, pancreatic and integral brush border enzymes in order to allow for sufficient nutritional uptake. Absorption and transport of dietary proteins across the epithelial layer is known to be dependent on the physicochemical properties of the proteins and their digestion fragments themselves, such as size, solubility and aggregation status. It is believed, that the greater an amount of intact protein or larger peptide fragments that is transported through the epithelial layer, and thus encountered by the mucosal immune system in the gut, the greater is the risk of inducing an adverse allergic response. Proteins may be absorbed across the epithelial barrier by means of various mechanisms, and studies have shown that a transcellular facilitated transport route unique for food allergic individuals are at play for transport of allergens, and that upon mediator release from mast cells an enhanced allergen transport via the paracellular route occurs. This is in contrast to healthy individuals where transcytosis through the enterocytes is the main route of protein uptake. Thus, knowledge on factors affecting intestinal barr