Gastrointestinal fate of food allergens and its relationship with allergenicity

Abstract

Food allergens are closely related to their gastrointestinal digestion fate, but the changes in food allergens during digestion and related mechanisms are quite complicated. This review presents in detail digestion models for predicting allergenicity, the fates of food allergens in oral, gastric and duodenal digestion, and the applications of digestomics in mapping IgE-binding epitopes of digestion-resistant peptides. Moreover, this review highlights the structure-activity relationships of food allergens during gastrointestinal digestion. Digestion-labile allergens may share common structural characteristics, such as high flexibility, rendering them easier to be hydrolyzed into small fragments with decreased or eliminated allergenicity. In contrast, the presence of disulfide bonds, tightly wound α-helical structures, or hydrophobic domains in food allergens helps them resist gastrointestinal digestion, stabilizing IgEbinding epitopes, thus maintaining their sensitization. In rare cases, digestion leads to increased allergenicity due to exposure of new epitopes. Finally, the action of the food matrix and processing on the digestion and allergenicity of food allergens as well as the underlying mechanisms was overviewed. The food matrix can directly act on the allergen by forming complexes or new epitopes to affect its gastrointestinal digestibility and thereby alter its allergenicity or indirectly affect the allergenicity by competing for enzymatic cleavage or influencing gastrointestinal pH and microbial flora. Several processing techniques attenuate the allergenicity of food proteins by altering their conformation to improve susceptibility to degradation by digestive enzymes. Given the complexity of food components, the food itself rather than a single allergen should be used to obtain more accurate data for allergenicity assessment.

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

“…Additionally, some pharmacological drugs (e.g., anti‐inflammatory compounds such as aspirin and diclofenac) might also impact the mechanism of allergen transportation, thus favoring paracellular transport over the transcellular routes. When modeling allergen transport, the digestibility of food proteins should thus be considered, and special attention should be paid to allergen structure following digestion to understand the potential interaction of digested allergens with intestinal epithelial cells (Sun et al., 2022). In this context, the impact of brush border enzyme activity should also be taken into account (Di Stasio et al., 2020).…”

“…Food processing as well as the food matrix can also have a major impact on digestion and subsequent transport of the nutrients through the intestinal epithelial barrier. Different processing methods may induce several physicochemical alterations on food proteins, including hydrolysis of peptide bonds, denaturation, aggregation by disulfide and noncovalent bonds, as well as potential food component interactions of the matrix, namely, lipids, carbohydrates, or other micronutrients (e.g., vitamins, minerals, polyphenols), which may affect the allergenic potential of proteins (Costa, Bavaro, et al., 2022; Costa, Villa, et al., 2022; Sun et al., 2022) (see Sun et al. [2022] for an excellent review).…”

“…The process of protein digestion starts in the stomach, where the main activators are hydrochloric acid and pepsin, and continues in the small intestine, where most of the protein digestion occurs through the action of the pancreatic enzymes. In the small intestine, peptidases tethered to the brush border membrane, such as aminopeptidases, carboxypeptidases, endopeptidases, and dipeptidases, complete peptide digestion by reducing them to di/tripeptides or free amino acids (Ozorio et al, 2020) (see Sun et al [2022] for an excellent review on the gastrointestinal fate of food allergens and its relationship with allergenicity). The majority of dietary proteins are fully converted into di/tripeptides and amino acids and are absorbed by the intestinal epithelial cells in the form of nutrients.…”

“…Food processing as well as the food matrix can also have a major impact on digestion and subsequent transport of the nutrients through the intestinal epithelial barrier. Different processing methods may induce several physicochemical alterations on food proteins, including hydrolysis of peptide bonds, denaturation, aggregation by disulfide and noncovalent bonds, as well as potential food component interactions of the matrix, namely, lipids, carbohydrates, or other micronutrients (e.g., vitamins, minerals, polyphenols), which may affect the allergenic potential of proteins (Costa, Bavaro, et al, 2022;Costa, Villa, et al, 2022;Sun et al, 2022) (see Sun et al [2022] for an excellent review). For instance, a food matrix with a high content of proteins can delay gastrointestinal digestion and the epithelial transport of food allergens, shaping their sensitizing capacity (Schulten et al, 2011).…”

On-chip immunomagnetic separation of allergens from myofibrillar proteins of seafoods for rapid allergy tests

“…That is, most of the food allergens are pepsin digestion-resistant proteins. 14 Simulated gastric fluid (SGF) digestion strategies have been developed to study protein allergens. Yu et al studied the allergenicity of large yellow croaker ( Larimichthys crocea ) proteins by analyzing the digests of the digestion-resistant proteins by reversed phase liquid chromatography coupled with tandem mass spectrometry (RPLC-MS/MS).…”