Growth and integrity of the small intestine in malnutrition and trauma

Abstract: The small intestine is an active metabolic organ constituting a functional and immunologic barrier to toxins and microbes in the intestinal lumen. Injuries are repaired by rapid cell replication, which depends on nutritional and humoral growth factors. Glutamine has been suggested to be the most important nutrient for the enterocytes. In the present studies, the effects of glutamine were evaluated using experiments with cultured cells and postoperative supplementation in animals and humans.Growth of two enterocyte-like epithelial cell lines, CaCo-2 and HT 29, was studied at different glutamine concentrations, and compared to effects of growth factors and energy substrates. Glutamine effects in starved, operated rats were evaluated by weight, DNA, protein analysis, 3H-thymidine incorporation in intestinal mucosa and urinary recovery of orally administered polyethylene glycols. Three different balanced and complete enteral preparations with no glutamine, 2% (normal) and 4% were used postoperatively . Growth parameters and tissue and plasma concentrations of humoral growth factors were studied 3 and 8 days after intestinal resection in the rat. In a clinical study with total parenteral nutrition for five days after major abdominal surgery, nitrogen balance and humoral growth factors in plasma were evaluated in patients receiving glutamine-containing dipeptide (Gly-Gln) amino acid solution, compared to conventional amino acid solution.In the cell cultures, glutamine was shown to be of importance both as a trophic factor and as a metabolic substrate, particularly in cells of intestinal origin. In the animal model of malnutrition and surgery, 3H-thymidine incorporation was higher in the supplemented group compared to glutamine-free and also higher in all operated groups compared to controls. The permeability study showed a higher uptake of small polyethylene glycol molecules in glutamine-supplemented animals, parallel to increases in thymidine incorporation. After major intestinal resection in rats, no major benefit on growth by glutamine supplementation could be found after one week. Rapid PYY increases in plasma and higher IGF-II concentration in ileal mucosa were found. Stimulation of IGF-II concentration suggested an auto- or paracrine action in regulating growth. In the clinical study, no significant differences were seen in the levels of transthyretin, retinol binding protein or nitrogen balance, compared to patients recieving conventional amino acid solution. A positive correlation between insulin and nitrogen balance was found inglutamine treated patients.It is concluded that glutamine has important effects as a nutritional substrate for enterocytes and stimulates their proliferation and absorptive capacity in refeeding after malnutrition and surgical trauma in the rat. After intestinal resection, glutamme has no major effects upon growth one week after surgery, but the production of growth factorsincreases earlier in glutamine supplemented animals. In clinical use, a glutamine supplemented amino acid solution appeared no better than conventional amino acd solution. It could, howeyer, represent a more balanced way of supportmg protem metabolism after trauma, by the interaction with insulin and other growth factors.