Isocaloric glutamine-free diet and the morphology and function of rat small intestine

Background: The importance of L-glutamine as metabolic fuel for enterocytes and its role in prevention of mucosal atrophy during total parenteral nutrition is well documented. No data are available to date that document whether a glutamine-free complete enteral diet, requiring full energy expenditure for hydrolysis and absorption, is associated with changes in the morphology and function of the small intestine. Our aim was to examine the effect of such a diet during a 4-week period on the morphology and function of the small intestine of rats. Methods: Three isocaloric solid rat food, containing 0%, 4%, and 8% of glutamate, respectively, were fed to three groups of rats. On the 7th and 28th days the morphology of the jejunum, the subcellular structure of enterocytes on transmission electron microscopy, enzyme activities, blood, and muscle glutamine were examined and compared in the three groups. Results: The rats on the glutamine-free diet had significantly lower mucosal wet weight, protein and DNA content, and number of intraepithelial lymphocytes on the 7th day, whereas the number of mitoses in the Lieberkuhn's crypts was significantly less on the 28th day. The height of the enterocytes and villi was 20% higher on average in the glutamine-free group. Electron microscopy revealed either early (swelling of cristae) or terminal (swelling of matrix) mitochondrial degenerative changes, homogenization of apical cytoplasm, and degeneration and fragmentation of microvilli with loss of their rootlets. The Na+,K+-ATPase activity was markedly decreased in the glutamine-free group compared with that of the other groups, most likely because of a diminished energy supply. Among brush border membrane enzymes, lactase activity decreased markedly (p <.05) in the first week. The glutamine-free diet resulted in an increase of the lung glutamine synthetase activity and decrease in muscle glutamine content by the 28th day of the diet. Conclusions: Our study shows for the first time that a complete enteral diet, deficient only in glutamine, is associated with significant early morphologic and functional changes in the small intestine. The precise effect on intracellular events and the time of onset of these changes needs to be clarified in the future.