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Title: The effect of defined formulae liquid diets on inflammatory bowel disease affected tissue
Author: Meister, Doris H. T.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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Inflammatory bowel disease is an incurable disease of the gastrointestinal tract of unknown aetiology. The two distinct types are Crohn's disease and ulcerative colitis. Both diseases have an imbalance of pro-and anti-inflammatory cytokines, such as interleukin-1β, interleukin-1ra and interleukin 10. Transforming growth factor beta (TGF-β) is upregulated in active disease, though upregulation also might contribute to mucosal healing and downregulation of inflammation. A treatment option which has been successfully used in Crohn's disease, alone or with corticosteroids, is nutritional therapy in the form of enteral defined formula diets, elemental or polymeric. This improves inflammatory activity as well as the nutritional status of the patient with Crohn's disease. In paediatric Crohn's disease patient's growth retardation may also be reversed. The actual mechanism by which liquid enteral diets improve inflammatory symptoms and heal the intestinal mucosal wall is not known. Hypotheses include exclusion of dietary antigens, improvement of nutritional status, alteration of bacterial flora, low lipid content and their low residue, reducing intestinal obstruction. The current study attempted to answer the question whether enteral diet and its modifications might directly influence the inflammatory response in intestinal tissue affected by inflammatory bowel disease. Intestinal endoscopic biopsies from patients with Crohn's disease, ulcerative colitis and control patients were incubated in an in-vitro organ culture model for 24 hours with elemental diet and modified enteral diets. The diets used were modified in nitrogen composition using casein or whey instead of amino acids in elemental diet. Other enteral diets were modified in fatty acid composition using fish oil, sunflower oil, safflower oil, canola oil, olive oil, fractionated coconut oil, unfractionated coconut oil and soya oil, but keeping the amino acid composition of elemental diet. The viability of tissue after 24 hours culture was established by bromodeoxyuridine uptake. Anti-and pro-inflammatory cytokines were measured in culture fluid by enzyme-linked immunoassay (ELISA) and anti-and pro-inflammatory cytokine ratios of IL1ra /IL1β and IL10/IL1β were used as a marker of in vitro inflammatory balance. In a further experiment biopsies were incubated with enteral diets containing colostrum and enteral diet containing whey extract enriched with TGF-β. Immunohistochemistry for TGF-β was performed to detect differences in TGF-V1 expression as a percentage of immunostained tissue area per mm². The results of these experiments show that enteral diets have a direct anti-inflammatory response in-vitro with an increase in anti-/pro-inflammatory cytokine ratio of IL1ra/IL1β and to some extent in IL10/IL1β. This response was different in Crohn's disease and ulcerative colitis affected tissue and was also dependent on the specific modified diet. Amino acid modified diets had an immuno-modulatory effect in Crohn's disease but not in ulcerative colitis and specific fatty acid modulated diets also produced disease and fatty acid specific response. Enteral diet modified by sunflower oil showed significant increases in the anti-/pro-inflammatory ratio in Crohn's disease and to some extent in ulcerative colitis, whereas incubation with enteral diet modified by fish oil was only anti-inflammatory in ulcerative colitis but not in Crohn's disease. The results also showed that diets containing growth factors, as in the case of colostrum and whey extract enriched with TGF-β, led to a significant upregulation in TGF-β expression in tissues affected with Crohn's disease but not with ulcerative colitis. These experiments have shown that amino acid and fatty acid modified diets can have a direct and disease specific impact on in-vitro intestinal inflammatory response in inflammatory bowel disease. Hence, by dietary modulation, it is possible to downregulate intestinal inflammatory response, and further adaptation of defined formulae diet is possible. It may also be possible to use some formulations to treat ulcerative colitis such as fish oil enriched diet, but further research into precise mechanisms of action and palatability is required.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available