Should digestion assays be used to estimate persistence of potential allergens in tests for safety of novel food proteins?

The adult human gastrointestinal tract (GI) is a tube approximately 9 meters long, running through the body from the mouth to the anus. The lumen of the GI tract is continuous with the external environment, keeping its contents outside of the rest of the body. The epithelial layer, which lines the interior of the GI tract, presents a partial barrier to invasion by ingested pathogens, parasites, toxins and antinutrients. If pathogens, toxins and food proteins breach the epithelium barrier, the immune system acts as our primary defense system. Antibodies are formed that specifically react with epitopes on certain antigenic proteins, and subsequent binding of subtypes of these antibodies to proteins can result in the mobilization of host defenses, including deleterious responses like allergy.The GI tract helps prevent food antigen penetration through its gut epithelial barrier. Epithelial cells are joined together with their neighbors via tight junctions and mucus produced by goblet cells [1]. In the upper bowel, the bulk of antigen exposure comes from foods, while in the lower bowel, the antigenic load comes from the complex microflora living in the GI tract. In addition to serving as a barrier, the mucosal system has two robust adaptive immune mechanisms to prevent general antigen circulation: (i) antigen exclusion mediated through the secretion of IgA and IgM antibodies to modulate the colonization of microorganisms and dampen penetration of soluble luminal agents, and (ii) suppressive mechanisms to avoid hypersensitivity to substances present in the mucosal surface [2]. The latter mechanism is known as oral tolerance when it is induced by food antigens [3].Despite these host defense mechanisms, antigens can be absorbed and distributed in the body. Intact food proteins can be detected in plasma [4-6] and gut bacteria can be detected in mesenteric lymph nodes [7]. An estimated 3 to 4% of adults and up to 8% of children suffer from food allergies in developed western