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Glutamine - Glutamine Effect on Gut Integrity

Glutamine Effect on Gut Integrity

Deborah J. Biondo, R.D.,L.D.,C.N.S.D.
Department of Dietetics and Nutrition
phone: (913) 588-7681
email: dbiondo@kumc.edu

Glutamine is one of the most abundant of the amino acids, and is found in all body tissues1. It has the highest concentration in whole blood (500-900 uM) of all amino acids2. The majority of glutamine is stored in the skeletal muscle, where its concentration is 30 times greater than the circulating level. In the basal state, skeletal muscle releases net amounts of glutamine, a process which accelerates during stress 3.

Glutamine has multiple functions. It is an essential precursor for nucleotide synthesis. It is a key fuel for intestinal mucosa, endothelial cells, renal tubular cells, lymphocytes and macrophages. Glutamine is also a substrate for renal ammoniagenesis3.

The enzyme glutaminase converts glutamine to glutamate and ammonium. Nearly all tissues possess glutaminase, yet the gut3 has the highest amount of glutaminase in the body. The enterocytes of the jejunum have the highest glutaminase activity of all tissues3.

Though considered to be a nonessential amino acid4, Glutamine is considered by some to be essential when the body is in a stressed state. The gut, as well as the kidney, seems to have a requirement for extracting large amounts of glutamine from circulation to support cellular metabolism and function. In many patients, the intestinal tract may be the initial septic source3.

In stress (such as sepsis, shock, and injury) there is an increased glutamine utilization, and usually decreased intake, of glutamine. Uptake of glutamine by the gut, kidneys, and lymphocytes during stress exceeds release, leading to depletion of total body glutamine stores. Consistent mobilization of glutamine stores contributes to prolonged stress. There is increased skeletal muscle proteolysis and translocation of amino acids from skeletal muscle to visceral organs. With prolonged stress, glutamine decreases in plasma and tissues. The gastrointestinal mucosa begins to atrophy5. The interorgan glutamine cycle5 is in operation. In states of stress, the following effects on the gut occur5:

    1. Increased permeability of intestinal mucosa
    2. Decreased host defense due to glucocorticoid administration or protein depletion
    3. Increased number of bacteria due to bacterial overgrowth

Breakdown of the gut mucosal barrier may occur and can result in the passage of luminal bacteria and endotoxins into the systemic circulation. Gut glutamine utilization falls during sepsis and endotoxemia. This impairment in gut glutamine utilization is associated with bacterial translocation and ultrastructural damage to the gut mucosa2.

Food ingestion is the dominant factor which allows the barrier function of the gut mucosa to be maintained. Enteral nutrition stimulates secretion of secretory IgA, growth and replication of the enterocytes, secretion of bile salts which neutralize endotoxin, and defecation (the gastrocolic reflex), which reduces the penetration of bacteria and endotoxins through the bowel wall. As a result of these functions, bacterial overgrowth in the intestinal tract does not occur, the barrier apparatus of the gut mucosa is preserved, bacterial translocation is prevented, and a healthy gut is maintained5.

Glutamine is present in some enteral feedings, but often in amounts too small to adequately support mucosal growth6. Current total parenteral nutrition (TpN) solutions do not contain glutamine due to its instability in aqueous solutions. Villous atrophy has been demonstrated in persons receiving long-term TpN. Animal studies have demonstrated that glutamine supplementation of TpN solutions resulted in an increase in jejunal mucosal weight and DNA content, and a significant decrease in the villous atrophy associated with standard hyperalimentation. provision of exogenous intravenous glutamine upregulates gut glutaminase activity and stimulates gut glutamine utilization. Bacterial translocation has been shown to decrease with glutamine-enriched TpN compared to standard TpN. The decrease in translocation was associated with normalization of S-IGA levels and decrease in bacterial adherance to enterocytes, suggesting that glutamine-supplemented TpN may enhance gut immune function. Studies have shown that glutamine-enriched enteral and parenteral formulas accelerate intestinal glutamine uptake7.

Addition of glutamine to the nutrition regimen, in stress may: Correct abnormally low glutamine concentrations in blood and tissues Increase cellularity of gut mucosa promote healing and bowel rescue (Diverticulitis) Support renal ammoniagenesis Support lymphocyte proliferation in response to bacterial translocation

Glutamine-supplemented diets in metabolically stressed patients may have a significant impact in the clinical setting. Human research in this area continues.

References

    1. Van Der Hulst, R., Van Kreel, B., Meyenfeldt, M., Brummer, R., Arends, J., Deutz, N., and Soeters, p. Glutamine and the preservation of gut integrity. Lancet 1993;341:1363-1365.
    2. Souba, W., Herskowitz, K., Austgen, T., Chen, M., and Salloum, R. Glutamine Nutrition: Theoretical considerations and therapeutic impact. JpEN 1990;14:237S-243S.
    3. Souba, W., Klimberg, V., plumley, D., et al. The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. J Surg Res 1990;48:383-391.
    4. Whitney, E. and Cataldo, C. Understanding Normal and Clinical Nutrition. West publishing Co., New York. 1983.
    5. Wilmore, D., Smith, R., O'Dwyer, S., Jacobs, D., Ziegler, R., and Wang, S. The gut: a central organ after surgical stress. Surgery 1988;104:917-923.
    6. Lo, C. and Walker, W. Changes in the gastrointestinal tract during enteral or parenteral feeding. Nutr Rev 19889;47:193-198.
    7. platell, C., McCauley, R., McCulloch, R., and Hall, J. The influence of parenteral glutamine and branced-chain amino acids on total parenteral nutrition-induced atrophy of the gut. JpEN 1993;17:348-354.
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