Title: Impaired Gut Barrier Function

Key words: leaky bowel syndrome, impaired absorption, malnutrition, parenteral feeding, enteral feeding, gut motility, taurine, glutamine

Date: July 2000

Category: 8. The Gut

Type: Article

Author: Dr van Rhijn


Impaired Gut Barrier Function

Leaky Bowel Syndrome



One of the major functions of the intestine is to form a barrier against lumenal micro-organisms and endotoxins. Critically ill patients, in a hyper metabolic state, requiring parenteral nutrition1, especially when combined with malnutrition and impaired immune function, are particularly at risk of developing impaired gut barrier function. Its consequences and nutritional support will be discussed below.

Consequences of an Impaired Gut Barrier

Impaired gut barrier function may lead to overgrowth of gut derived2,3 micro-organisms. The subsequent endotoxin-induced4 liver dysfunction (depressed Kupffer cell function5) is a risk factor for impaired systemic immunity (RES), leading to sepsis6 and multisystem organ failure7. Colonic enterocytes lose their protective barrier function and increased intestinal permeability8 allows microbial translocation (and endotoxins) from the epithelial mucosa into mesenteric lymph nodes9 and circulation. Low-level pathogens only cause morbidity, whilst potentially pathogenic microorganisms also cause mortality10.

However, systemic endotoxaemia (septicaemia) only occurs in those who already carry abnormal flora, indicating gut overgrowth, thus a carrier state is a marker for the severity of the underlying disease11. Sepsis may result in liver failure, multi perfusion injury, subsequent free radical damage and multisystem organ failure that pose a difficult nutritional challenge, especially because impaired absorption of essential nutrients (especially essential amino acids12 due to hypoplasia) further contributes to deterioration of the disease.

Nutritional Support Measures

The presence of gut lumen nutrients is the most important stimulus for intestinal growth and function13. Enteral feeding14 at the earliest15 opportunity is the best support for in maintaining mucosal structure and function16, strengthening local & systemic immune defences by re-establishing gut motility17 and gall bladder contractility18. It is safe and efficient19 and allows for providing specialized immune-modulating nutrition support20. Gut protection can be further enhanced by taurine & glutamine21, essential nutrients for the mucosal enterocyte22, having trophic23, 24 effects on the gut (increased villus height and decreased gut permeability25) and maintaining function of rapidly proliferating cells such as lymphocytes (immuno-enhancing26). Epidermal growth factor27 and short chain fatty acids28 exert a trophic effect on the small intestine and colonic mucosa respectively and cholecystokinin reduces cholestasis29. Other immuno-modulatory nutrients include arginine30, RNA31, n-3 essential fatty acids32, ornithine a -ketoglutarate33 and antioxidants to reduce septic complications, speed up recovery34 and increase survival35 in the critically ill. Branched chain amino acid-enriched enteral formula may aid liver recovery36.



Critical illness has a variety of effects on intestinal mucosa and the most practical approach for bowel protection is to maximize enteral37 immuno-enhancing nutritional38 supplements to stimulate mucosal growth and promote gut health. Nutritional pharmacology has come of age.


  1. Li, J. et al. Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue. J. Trauma. 1995; 39: 44 – 52.
  2. Pierro, A. et al. Microbial translocation in neonates and infants receiving long-term parenteral nutrition. Arch. Surg. 1996; 131, 176 – 179.
  3. Reynolds, J.V. et al. Impaired gut barrier function in malnourished patients. Br. J. Surg. 1996; 83:9, 1288 – 1291.
  4. van Saene, H.K.F. et al. Selective decontamination of the digestive tract contribute to the control of disseminated intravascular contamination in severe liver impairment. J. Ped. Gastroent. Nutr. 1992; 14: 436 – 442.
  5. Van Leeuwen, P.A. et al. Clinical significance of translocation. Gut. 1994; 35:1 (Suppl): S28 - S34.
  6. Alverdy, J.C. & Burke, D. Total parenteral nutrition: iatrogenic immunosuppression. Nutrition. 1992; 8: 359 – 365.
  7. Gardiner, K.R. et al. Novel substrates to maintain gut integrity. Nutr. Res. Rev. 1995; 8: 43 – 66.
  8. Johnston, J.D. et al. Gastrointestinal permeability and absorptive capacity in sepsis. Crit. Care Med. 1995; 24: 1144 – 1149.
  9. Ferri, M. et al. Bacterial translocation during portal clamping for liver resection. Arch. Surg. 1997; 132: 162 – 165.
  10. van Saene, H.K.F. et al. How to classify infections in intensive care units. The carrier state, a criterion whose time has come? J. Hosp. Infec. 1996; 33: 1 – 12.
  11. Donnell, S.C. et al. Nutritional implications of gut overgrowth and selective decontamination of the digestive tract. Symposium on ‘Nutrition and gut barrier function’. Proc. Nutr. Soc. 1998; 57: 381 – 387.
  12. Gardiner, K.R. et al. Failure of intestinal amino acid absorptive mechanisms in sepsis. J. Am. Coll. Surg. 1995; 181:431 – 436.
  13. Lara, T.M. Effect of critical illness and nutritional support on mucosal mass and function. Clin. Nutr. 1998; 17: 99 – 105.
  14. Minard, G. & Kudsk, K.A. Effects of route of feeding on the incidence of septic complications in critically ill patients. Semin. Resp. Infect. 1994; 9: 228 – 231.
  15. Kompan, L. et al. Effects of early enteral nutrition on intestinal permeability and the development of multiple organ failure after multiple injury. Intensive Care Med. 1999; 25:2, 157 – 161.
  16. Bragg, L.E. et al. Influence of nutrient delivery on gut structure and function. Nutrition. 1991; 7:4, 237 – 243.
  17. Hadfield, R.J. et al. Effects on enteral and parenteral nutrition on gut mucosal permeability in the critically ill. Am. J. Respir. Crit. Care Med. 1995; 152: 1545 – 1548.
  18. Jawaheer, G. et al. gall bladder contractibility in neonates: effects of parenteral and enteral feeding. Arch. Diseases Childhood. 1995; 72: F200 – F202.
  19. Mainous, M.R. et al. Nutritional support of the gut: how and why. New Horiz. 1994; 2:2, 193 – 201.
  20. Culpepper Morgan, J.A. et al. Using enteral nutrition formulas. Gastroenterologist. 1993; 1:2, 143 – 157.
  21. Griffiths, R.D. et al. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition. 1997; 13: 295 - 302.
  22. Scheppach, W. et al. Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon. Gastroent. 1994; 107: 429 – 434.
  23. van der Hulst, R.R et al. Glutamine: an essential amino-acid for the gut. Nutrition. 1996; 12: 578 – 581.
  24. van der Hulst, R.R et al. Glutamine and the preservation of gut integrity. Lancet. 1993; 341: 1363 – 1365.
  25. Hall, J.C. et al. Glutamine. Br. J. Surg. 1996; 83: 305 – 312.
  26. Wilmore, D.W. & Shabert, J.K. The role of glutamine in immunologic responses. Nutrition. 1998; 14: 618 – 626.
  27. Fürst, P & Rombeau, J.L. growth factors and the intestine in critical illness. In: Rombeau, J.L. & Takala, J. Gut Dysfunction in Critical Illness. Berlin: Springer Verlag. 1996. pp. 375 – 393.
  28. Jolliet, P. et al. Enteral nutrition in intensive care patients: a practical approach. Clin. Nutr. 1999; 18, 1: 47 – 56.
  29. Rintala, R.J. et al. Total parenteral nutrition-associated cholestasis in surgical neonates may be reversed by intravenous cholecystokinin: a preliminary report. J. Pediat. Surg. 1995; 30: 827 – 830.
  30. Braga, M. et al. Artificial nutrition after major abdominal surgery: impact route of administration and composition of diet. Crit. Care Med. 1998; 26: 24 – 30.
  31. Kemen, M. et al. early postoperative enteral nutrition with arginine, w -3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of impact. Crit Care Med. 1995; 23: 652 – 659.
  32. Bower, R.H. et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides and fish oil in intensive care unit patients: results of a multicenter, prospective, randomised clinical trial. Crit. Care Med. 1995; 23: 436 – 449.
  33. Le Bricon, T. et al. Ornithine a -ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion. Am. J. Clin. Nutr. 1997; 65: 512 – 518.
  34. Kudsk, K.A. et al. A randomised trial of isonitrogenous enteral diets after severe trauma: an immune-enhancing diet reduces septic complications. Ann. Surg. 1996; 224: 531 – 542.
  35. Jones, C. et al. Randomized clinical outcome study of critically ill patients given glutamine- supplemented enteral nutrition. Nutrition. 1999, 15: 108 - 115.
  36. Fisher, J.E. & Kane, T.D. Nutrition in Liver Disease. In: Ziegler E. & Filer L. Present knowledge in Nutrition. Seventh Edition. ILSI Press. Washington. 1996; Chapter 47 pp 472 – 481.
  37. Pennington, C.R. Intestinal Failure and Artificial Nutritional Support. Proc. R. Coll. Physicians Edinb. 1997; 27: 418 – 431.
  38. Barton, R.G. 1997. Immune-enhancing enteral formulas: are they beneficial in critically ill patients? NCP. 12(2): 51 – 62.