Food Structure and Health
Transport and Uptake Processes
Primary Objectives
- Understand how colloidal and biopolymeric food structures affect the uptake of biologically active macromolecules (including bioactive polysaccharides and food allergens) across the mucus and epithelial layers of the gut mucosal barrier, particularly in the small intestine.
- To investigate the immune modulating effect of the key structures surviving digestion in the lumen and that stimulate responses via direct interaction with the gut epithelium and through differential routes of uptake across the epithelial barrier, particularly in relation to allergenicity.
For the body to make use of the nutrients made available by digestive processes they must be transported from the GI tract lumen and into the lymphatic system or the blood stream. Depending on the size of the components involved this can occur through a number of possible routes, such as via enterocytes or a para-cellular route between the enterocytes or via M-cells. However, for most of these routes transport through the protective mucin layer is a prerequisite. If we are to be able to effectively deliver bioactive compounds from food or pharmaceuticals, especially in a particulate or encapsulated form, then an understanding of the heterogeneity and biophysical attributes of the mucin layer is vital.
The mucin layer comprises a heterogeneous mixture of peptidoglycans (the mucins), partly digested nutrients, enzymes, cellular material, etc. The physical properties of this layer are largely defined by the architecture of the mucin complexes. Mucus structures occupy a range of length scales from the nano-scale of the rigid and flexible parts of the individual mucin polypeptides to the micro-scale of the tightly or loosely adherent layers of the polymer. Whilst rheological properties of the mucin can provide information about the strength of the network and thus diffusion, they depend on the scale of the measurement. Thus, on the macroscopic scale bulk rheological properties are relevant, whilst on the molecular scale the porosity of the network becomes important and thus the micro-rheology is the key parameter. Bulk rheology has shown that mucus is a viscoelastic polymer but so far only very limited measurements of the micro-rheology of mucus have been reported and none of these are on GI tract mucus.
Non-specific interactions are important for the transport/motility of small particles such as lipid droplets, micelles, nano-particles and bacteria across the mucin layer. We have a wealth of experience in looking at these types of colloidal problems in food systems and we are building on this to investigate transport and uptake in the GI tract. The electrostatic nature of mucin is important in conferring physical properties and is determined by both amino acid composition and the presence of O-linked glycans including terminal sugars such as sialic acid and sulphated glycans. Another important feature is the large size of the gel-forming mucin polypeptides, which are some of the largest proteins to have ever been sequenced, with a molecular weight >1MDa. Also, pH has an important effect on mucin-mucin interactions affecting the rheological and gel-forming properties of mucus.
Adhesive interactions play a role in the diffusion of particulates through the mucus layer. Whether these are electrostatic or hydrophobic in nature depends on the type and complexity of the particulate, e.g. food particles or bacteria. The precise nature of mucoadhesion of bacteria in the GI tract has not been defined and many studies have used mucin purified from faecal samples (Kirjavainen, 1998) that may be of limited relevance to what happens in vivo because of the degraded nature of faecal mucus. These studies have not only shown differences in adhesion between different strains but also between mucin samples from patients of different ages. For Helicobacter binding, both in the oral cavity and the gastric compartment, four different mechanisms have been identified involving a combination of both specific receptor mediated interactions and non-specific charge interactions.
|
Confocal micrograph of a protein stabilised emulsion following gastric and duodenal digestion adhering to a layer of scraped mucous. The physiological conditions and emulsion preparation are varied to determine the effect on the interactions with mucous layer. |
 |
This research is undertaking a combined study of both the mucus layer and the underlying epithelium, drawing on research activity undertaken elsewhere within IFR. Studies on mucus interactions focus on non-specific interactions and are complementary to the work of Nathalie Juge investigating specific interactions.
Fax: +44(0)1603 507723 
