Intestinal permeability in animal models of SBS has been determined selleck bio by ex vivo electrophysiological methods and in vivo studies of paracellular permeation of luminal nonmetabolizable sugar markers (24, 27, 32, 33, 37, 39, 41). However, the results of these studies have been conflicting, and permeability studies do not always correlate with concomitant bacterial translocation (24, 27, 32, 33, 37, 39, 41). Another possible cause of impaired gut barrier function in SBS may be net loss of gut-associated lymphoid tissue (GALT) after massive partial small bowel and/or colonic resection. Available data from animal models indicate that some components of GALT (e.g., T4 and T8 cell number; T4/T8 ratio) and humoral immune function (systemic B cells and immunoglobulins, mucosal plasma cells) are decreased after massive small bowel resection (4, 10, 30).
Most of these observations were made within 1�C2 wk after operation. However, bacterial translocation from the gut lumen may elicit adaptive immune responses that develop over a longer time frame, such as secretion into the gut lumen of secretory IgA (sIgA) by mucosa plasma cells. Glutamine (GLN) is a major fuel substrate for both intestinal epithelial and circulating and fixed immune cells (2, 20, 42, 43). This amino acid is an important substrate for synthesis of purines and pyrimidines, ammonia, glucose, and amino acids and has several other major metabolic functions (20, 43). In addition, GLN inhibits apoptosis and stimulates cell proliferation in both intestinal and immune cells (12, 14, 16, 42).
Such functions may be crucial for GALT activation in response to bacterial invasion. Dietary or intravenous GLN supplementation inhibits AV-951 bacterial translocation in a number of catabolic animal models with intact intestine (5�C6, 8, 11, 13, 15, 17, 40). GLN may become a conditionally essential nutrient during catabolic stress owing to the increased need for this substrate by gut epithelia, concomitant with insufficient cellular capacity for endogenous GLN production (21, 35, 43). The present study was designed to contrast the effect of dietary GLN supplementation and oral antibiotic administration on indexes of gut barrier function in a rat model of combined partial small bowel-colonic resection, a previously utilized translational model for human SBS. METHODS Animals. Young (6 wk) male Sprague-Dawley rats (Charles River Laboratories, Wilmington, MA) were used. The rats were housed in individual cages in the animal care facility under controlled conditions of temperature and humidity with a 12-h light, 12-h dark cycle. The animals were given free access to water and standard pelleted rat food (Laboratory Rodent Chow 5001, PMI Feeds, St. Louis, MO) during a 7-day acclimation period.