The morbidity of inflammatory bowel disease (IBD) stems from its effect on electrolytes, nutrients and fluid absorption; thus, patients with IBD sustain malabsorption and diarrhea with attendant malnutrition and weight loss. Therefore, the goal of medical treatment of IBD has been to modulate the chronic intestinal inflammation to minimize the morbidity, namely the malabsorption of electrolytes, nutrients and fluid. However, the mechanisms of intestinal absorption and secretion in the IBD intestine are incompletely understood because of the lack of suitable animal models of chronic small intestinal inflammation and the inability to isolate the functionally different absorptive villus and secretory crypt cells from the chronically inflamed intestine. Given this background, the investigators developed a rabbit model of chronic small intestinal inflammation which duplicates the numerous electrolyte and nutrient transport alterations characteristic of IBD. The investigators then focused on two transport processes which are essential for both electrolyte and nutrient absorption: Na-glucose co-transport (SGLT-1) and Na-amino acid co-transport (NacT). The investigator's studies demonstrated that these transporters are uniquely affected during chronic enteritis. It is possible to significantly attenuate the inhibition of these transporters by immune modulation of the inflammatory process. Further, the investigators have determined that prostanoids mediate the effect on SGLT-1 whereas leukotrienes affect NacT in the chronically inflamed intestine. These observations have led the investigators to hypothesize that immune-inflammatory mediators generated by the cyclooxygenase and lipoxygenase pathways are responsible for the changes in SGLT-1 and NacT in the chronically inflamed intestine. Thus, the overall goal of this proposal is to determine the regulation of SGLT-1 and NacT during chronic enteritis. This study will demonstrate that there is active regulation of essential Na-nutrient co-transport processes in the chronically inflamed intestine. It will provide new insights into the exact mechanisms of alteration of these important transporters during chronic enteritis. Finally, better understanding of the regulation of Na-dependent nutrient co-transport processes in the chronically inflamed intestine will provide the basis for new and more efficacious treatment modalities for the malabsorption, diarrhea and malnutrition of IBD.
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