Glutamine Prevents Parenteral Nutrition‐Induced Increases in Intestinal Permeability

Abstract

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. This study evaluated changes in rat jejunal permeability and histology after total parenteral nutrition (TPN) or TPN supplemented with glutamine. Lactulose and mannitol were used to measure jejunal permeability, and fixed stained histologic specimens were used to measure mucosal dimensions. After the insertion of central venous catheters, 18 male rats were randomly divided into three groups: CHOW, saline infusion with a standard laboratory rat diet ad libitum; TPN; and GLN, 2% L-glutamine-supplemented TPN. The TPN and GLN groups received isocaloric, isovolumic, and isonitrogenous feedings. After 7 days of infusion, a laparotomy was performed, and lactulose and mannitol were instilled into the lumen of a 25-cm ligated segment of jejunum. Urine was collected for 5 hours and assayed for lactulose, mannitol, and creatinine. The jejunum was harvested, and wet weight, villus height, mucosal thickness, and villus width were measured. Intestinal permeability to lactulose and the lactulose to mannitol ratio significantly increased after TPN compared with CHOW, and these effects were prevented with the addition of glutamine to the TPN solution. Jejunal villus height and mucosal thickness significantly decreased following TPN but were not significantly different from CHOW when glutamine was added to the TPN solution. These data suggest that TPN was associated with increased jejunal permeability and that glutamine, when added to the TPN solution, prevented this effect. In addition, glutamine reduced TPN-associated atrophy of the jejunum.

Low Intestinal Glutamine Level and Low Glutaminase Activity in Crohn’s Disease: A Rational for Glutamine Supplementation?

“…The capacity of intestinal epithelial cells to synthesize glutamine is limited because of low glutamine synthetase activity [11], whereas muscle is a major organ of glutamine production and storage [3]. Intestinal mucosal atrophy, increased gut permeability, and mucosal hypofunction rapidly develop in animals after standard glutamine-deficient total parenteral nutrition [12][13][14][15], glutamine-free diet [16], or starvation [17]. Whether similar changes occur in humans remains controversial [18].…”

“…Nutritional support for the gut by glutamine supplementation stimulates mucosal cell growth to aid repair of mucosal injury and improve the intestinal structure and function [12][13][14][15][16][17]. Furthermore, glutamine has been shown to be of benefit in methotrexate-induced enterocolitis [19,20] and to protect the intestinal mucosa from radiation injury [21,22].…”

Effects of percutaneous endoscopic gastrostomy tube placement on gastric antral motility and gastric emptying

“…27,28 It has also been reported that TPN results in bacterial overgrowth, 29,30 increased intestinal permeability, and bacterial translocation. [29][30][31][32][33] Administration of TPN has been associated with a high incidence of septic morbidity, pneumonia, intraabdominal abscess, liver injury, and multiple organ failure. 7,8 Therefore, enteral nutrition is the preferable and physiological nutritional route.…”

Specific topics and complications of parenteral nutrition

“…What seems clear, however, is the beneficial effect of glutamine in the TPN formula to reverse and prevent the increase in intestinal permeability, as well as to maintain the exocrine function of the pancreas by preserving the integrity of the acinar cells [64,71,72].…”