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Mechanisms of food intolerance: relationship between gut mucosal integrity, allergy and adverse reactions

Obiettivo

The objective of the project is to achieve a better understanding of the role of bioactive food constituents on the induction and elicitation of allergic reactions to food proteins.
Research was carried out in order to achieve a better understanding of the role of bioactive food constituents on the induction and elicitation of allergic reactions to food proteins.
Specific immunoglobulin E (IgE) antibody responses to a series of purified milk allergens have led to a description of the distribution of IgE responses in individuals allergic to cow's milk. Also, the enzyme linked immunosorbent assay (ELISA) has been modified by the use of biotinoligated peptides in order to study the allergenicity of hydrolysed milk allergens.

BN rat was found to produce IgE responses to a variety of milk proteins. The effect of oral challenge on the elicitation of a local allergic reaction in the gut was examined using an intestinal extravasation assay and an assay to detect rat mast cell protease (RMCP II) in serum has been developed.
A treatment regimen for sensitization of BN rats via the oral route using ovalbumin has been identified. Studies have demonstrated differences in the specificity of antibody responses to semiskimmed milk proteins following sensitization by either route.

Fractionation isolations, characterization and in vitro screening of bioactive food constituents have been carried out and foods have been screened to determine the presence and level of bioactive agents. It has been confirmed that compounds which cause depolarization and increased gastrointestinal permeability in vitro also lead to a rise in mucosal permeability to macromolecules.

The in vitro activity of bioactive compounds were tested on rat intestinal epithelial cell lines and human intestinal cell lines. The human derived cell appeared less sensitive than the rat derived cell lines and the glycoalkaloid mixture appeared more active than saponin with a cytotoxic potency comparable to that of alpha-tomatine. Acute toxicity studies with the above bioactive agents in BN rats revealed treatment related changes in the stomach, duodenum, and body weight. Studies on the effect of alpha-tomatine on gut permeability have also been carried out.
To achieve these objectives the project was divided into four separate but complementary areas of activity, utilising specifically developed expertise. The following work programme was instituted:

1. To isolate and characterise biologically active food constituents (e.g. glycoalkaloids from potato tubers, alpha-tomatine, saponins from plant and vegetable material), their ability to modify the intestinal tract would be ranked in vitro, by determining their effect on mucosal permeability and their direct effect on gut epithelial cell line function;

2. Constituents active in both systems would then be ranked in terms of in vitro effects on rat gut mucosal permeability after short-term feeding studies;

3. To establish an experimental animal model of food allergy where the responses were comparable to those found in allergic human patients;

4. To choose a well known common allergen (milk) in order to perform clinical studies. Such studies would yield important information on the range of responses found in human patients and enable identification and isolation of potentially allergenic components present in milk. The studies would also permit a comparison with experimental data;

5. To utilise the information gained from 1-4 to determine the relationship between increased gut permeability and induction or elicitation of allergic reactions to milk proteins.

The successful completion of these objectives should lead to a better understanding of food intolerance, benefit both the consumer and the food industry.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.

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Coordinatore

Bibra International
Contributo UE
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Indirizzo
Woodmansterne Road
SM5 4DS Carshalton
Regno Unito

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