Role of glutamine in bacterial transcytosis and epithelial cell injury

Abstract

Background: L-Glutamine is the principal energy source for small intestinal enterocytes. Diminution of intestinal function, mucosal atrophy, and increased bacterial translocation have been noted during total parenteral nutrition (TPN). In a rat model of glutamine starvation, we previously showed that luminal glutamine is essential for optimal intestinal function. In this study, we examined the effect of apical vs basolateral glutamine on bacterial translocation in a Caco-2 cell culture system and bacteria-induced tissue injury in a weanling rabbit ileal loop model.

Methods: Caco-2 cells were grown in a transwell system. After confluence, apical and basolateral chambers received defined media, and glutamine deprivation was carried out over a 4- to 48-hour period. Escherichia coli transcytosis and structure/function studies were then performed. In a second series of experiments, the effect of intraluminal glutamine supplementation was evaluated in an E. coli-induced tissue injury model in weanling rabbit ileal loops.

Results: Expression of disaccharidases, glucoamylase, and Na+/K(+)-adenosine 5'-triphosphatase (ATPase) were significantly reduced when cells were deprived of glutamine from the apical side, and there was increased bacterial translocation across the monolayer. Transepithelial epithelial resistance (TEER) across the monolayer was also reduced in the glutamine-free cultures. Glutamine replenishment over 24 to 48 hours restored the original functions. Basolateral deprivation had a smaller effect on the Caco-2 cells. Typical necrotic mucosal injury caused by E. coli in the ileal loops was blocked by co-infiltration of the loops with glutamine.

Conclusions: This study demonstrates for the first time that the supply of glutamine from the apical side is of critical importance for maintaining optimal structure and function of the enterocytes. The effects are not acute or energy related. These observations have important clinical implications in the management of patients under critical care, including premature infants and patients receiving TPN, for whom lack of glutamine from the luminal side could produce mucosal dysfunction, resulting ultimately in severe atrophic/necrotic complications.