Gastrointestinal absorption of intact proteins.

There is now no reasonable doubt that small quantities of intact proteins do cross the gastrointestinal tract in animals and adult humans, and that this is a physiologically normal process required for antigen sampling by subepithelial immune tissue in the gut. It is too small to be nutritionally significant in terms of gross acquisition of amino-nitrogen, but since it has important implications relating to dietary composition it must receive consideration from nutritionists. The process of intact protein absorption occurs without eliciting harmful consequences for most individuals, but it appears likely that a small number of people absorbing these "normal" amounts may react idiosyncratically; also, some individuals may absorb excessive amounts, and they may suffer clinically significant consequences. Likewise, individuals with diminished absorption of intact protein may be at risk. Normal absorption probably occurs predominantly by transcellular endocytosis with some possible contribution by a route between cells; increased net entry of protein to the circulation may reflect (a) increased paracellular (intercellular) passage, (b) increased transcellular passage, and/or (c) decreased lysosomal proteolysis. Tests to distinguish among these possibilities are strongly desirable. Intact protein absorption may be involved in the pathogenesis of inflammatory bowel disease, "food allergies," and other diseases, including even major psychiatric disorders, but the current evidence is mainly indirect and suggestive. Great caution and careful objective studies are needed to establish whether such relationships with disease do exist and to unravel the underlying basic physiological mechanisms. Now that interest has developed in the assessment of intestinal permeability to small- and medium-sized molecules, it is hoped that equally simple methods for studying macromolecular permeability will be developed and applied. Therapeutic methods for enhancing intact polypeptide absorption would be valuable for vaccine and peptide drug administration by the oral route. Therapeutic reduction of the process may be relevant in food-sensitive patients.