Mucosal barrier presence

The infant immune system is not fnlly mature at birth it has deficits in the ability to prevent invasion of pathogens and to respond to antigens. Of particular concern in the context of ingredients new to infant formulas is the increased permeability of the gut mucosal barrier in the presence of inflammation or infection or if the integrity of the epithelial cell layer is disrupted. The increased permeability allows macromolecules to be absorbed, which stimulates allergic responses to food proteins. 

Ischaemia and the presence of acid are the prerequisite pathogenic features. The gastric mucosal barrier in such patients is often highly permeable to acid and this phenomenon may also contribute significantly to the production of these lesions. ... 

Abstract The major enzymatic barrier to the absorption of macromolecules, particularly therapeutic peptides, is the pancreatic enzymes the peptidases, nucleases, lipases and esterases that are secreted in considerable quantities into the intestinal lumen and rapidly hydrolyse macromolecules and lipids. In the case of the peptidases, they work in a co-ordinated fashion, whereby the action of the pancreatic enzymes is augmented by those in the brush borders of the intestinal cells. The sloughing-off of mucosal cells into the lumen also furnishes a mixture of enzymes that are a threat to macromolecules. As the specificity and activity of the enzymes are not always predictable, during pharmaceutical development it is important to test the stability of therapeutic macromolecules, and novel macromolecular-containing or lipid-containing formulations, in the presence of mixtures of pancreatic enzymes and bile salts, or in animal intestinal washouts or ideally, aspirates of human intestinal contents. 

Recently, the role of the UWL as a major diffusion limitation has been questioned[28,29]. It is known that the mucosal surface is coated with micropolysaccharides (mucins) secreted by goblet cells and epithelial cells[29]. The structural and functional importance of these mucins have been reviewed elsewhere[29]. It has been suggested that this mucin layer may, in fact, represent a major diffusion barrier in the intestine, and can account for the phenomena attributed to the UWL[28]. Our own studies[52] have indicated that cholesterol is extensively bound to an intestinally-derived sialomucin, and this interaction severely limits transmembrane translocation of the sterol. However, in the presence of simple or mixed micelles containing taurocholate, this mucin is solubilized and released from the surface, cholesterol absorption to the surface is diminished, and membrane translocation of the sterol is dramatically increased (Table 2). 

---