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Protein synthesis and gastrointestinal pathophysiology in a piglet model of colitis: Importance of nutrition and probiotics

Posted on:2008-10-18Degree:Ph.DType:Thesis
University:McGill University (Canada)Candidate:Harding, Scott VFull Text:PDF
GTID:2444390005472365Subject:Health Sciences
Abstract/Summary:
Objectives. Adequate nutrition and probiotics have both been shown to reduce the severity of colitis but their impact on hepatic and gastrointestinal protein metabolism has not been studied. Our primary objective was to compare the independent effect of probiotics vs. providing adequate nutrition on protein synthesis in a macronutrient-restricted piglet model of colitis. The secondary outcomes of this study were to determine histological contrasts and changes in oxidative stress markers resulting from probiotics in the malnourished state or providing adequate nutrition. Finally, we also measured mass balance and plasma concentrations of copper, iron and zinc over 5 days of colitis to determine how trace element nutrition is impacted by both colitis and probiotics. Design and Analysis. Twenty-four piglets, receiving lg·kg-1·d-1 dextran sulphate (DS), were randomized to receive a 50% macronutrient restricted diet without (MR) and with probiotics (MR+PRO) or a diet providing 100% NRC requirements for growing piglets (WN). Eight other piglets were randomized into a well-nourished group without colitis (REF) for histological and trace element comparisons. A primed constant infusion of the tracer L-[ring-2H5]phenylalanine was performed to determine the protein synthesis in small intestinal mucosa, colon, liver and of plasma proteins. Standard, in situ and immunohistological staining techniques were used for histological assessment and the ferric reducing antioxidant power assay, ELISA F2-isoprostane assay and plasma copper:zinc ratio were used as oxidative stress markers.;Conclusions. While probiotics did not appear to affect the gut (protein synthesis or colitis severity), a clear signalling mechanism between the gut and liver would appear to be responsible for the stimulation of liver protein synthesis. A strategy for correcting compromised nutrition appears to be more beneficial than using probiotics only for reducing damage during colitis accompanied by mild malnutrition.;Results. Providing adequate nutrition increased protein synthesis in colon, liver and plasma albumin pool and decreased colitis severity. Probiotics stimulated protein synthesis in the liver as well as synthesis of all liver-derived plasma proteins, without affecting GI protein synthesis. Iron and zinc appear to be affected by both colitis and colitis with superimposed malnutrition but copper status was unaffected.
Keywords/Search Tags:Colitis, Nutrition, Protein synthesis, Probiotics
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