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

Abstract

Intestinal glutamine utilization is integral to mucosal regeneration. We analyzed the systemic and intestinal glutamine status in Crohn's disease (CD) and evaluated the therapeutic effect of glutamine supplementation in an animal model of ileitis. In CD, glutamine concentrations were decreased systemically and in noninflamed and inflamed ileal/colonic mucosa. Mucosal glutaminase activities were depressed in the ileum independent of inflammation but were not different from controls in the colon. In experimental ileitis, oral glutamine feeding prevented macroscopic inflammation, enhanced ileal and colonic glutaminase activities above controls, and normalized the intestinal glutathione redox status. However, glutamine supplementation enhanced myeloperoxidase activity along the gastrointestinal tract and potentiated lipid peroxidation in the colon. In conclusion, glutamine metabolism is impaired in CD. In experimental ileitis, glutamine supplementation prevents inflammatory tissue damage. In the colon, however, which does not use glutamine as its principal energy source, immune enhancement of inflammatory cells by glutamine increases oxidative tissue injury.

Potential for amino acids supplementation during inflammatory bowel diseases

“…6 Nevertheless, glutamine mucosal content is decreased in noninflamed and more markedly depleted in inflamed ileum and colon from CD patients undergoing surgery compared with a control population. 7 As glutamine is the preferred substrate for both enterocytes and other rapidly dividing cells, such as immune cells, these data suggest a potential beneficial role for glutamine supplementation. Glutamine has been described to have beneficial effects on the clinical outcome of critically ill patients through several mechanisms including antiinflammatory effects, induction of heat shock proteins, support of antioxidant defenses, and modulation of intestinal proteolysis.…”

Does active Crohn's disease have decreased intestinal antioxidant capacity?

“…Lower concentrations of glutathione can be associated with decreased bioavailability of the substrate or reduced activity of its enzyme synthesis 52,53 due to many factors, including malnutrition. 33 Nutritional imbalance cannot explain decreased levels of GSH T found in inflamed mucosa in our population due to the fact that no significant weight loss was found in CD patients and no correlation between BMI and concentrations of GSH and GSH T was detected.…”

A Diet Containing Whey Protein, Glutamine, and TGFβ Modulates Gut Protein Metabolism During Chemotherapy-Induced Mucositis in Rats

“…CP provides whey proteins that are rich in cysteine, the rate-limiting amino acid for the synthesis of GSH. In addition, CP also contains glutamine, which increases the intestinal GSH content in different models [7,11,32]. In normal tissues, toxicity due to chemotherapy is enhanced when GSH stores are depleted.…”

“…Glutamine, considered as a conditionally essential amino acid, is the preferential substrate for enterocytes. During intestinal inflammation, the mucosal content of glutamine is reduced [7]. Moreover, glutamine stimulates intestinal protein synthesis [8], stimulates enterocyte proliferation [9] and exerts anti-inflammatory effects [10].…”