Immunomodulatory Effects of Enteral Nutrition
World Small Animal Veterinary Association World Congress Proceedings, 2009
Márcio Antonio Brunetto, DVM, MS, PhD Student; Aulus Cavalieri Carciofi, DVM, MS, PhD
Clinical Nutrition Service, Teaching Veterinary Hospital of the São Paulo State University, Jaboticabal-SP, Brazil


Enteral nutritional therapy is defined as supplying nutrients to the lumen of the gastrointestinal tract, given by mouth, tubes or ostomies, with the objective of maintaining or recovering the nutritional status of a patient. Whenever possible, the use of enteral nutritional support is preferable to parenteral, as it is more physiological, safer, and cost effective. It also ensures that nutrients will be available in the intestinal lumen, maintaining the integrity of the mucosa, preventing bacterial translocation. The presence of nutrients in the intestinal lumen represents an important trophic stimulation for the gut mucosa. The absorption of nutrients from the intestinal lumen meets 70% of the energy requirement of colonocytes and 50% of enterocytes requirement, the remaining amount being provided by the blood stream. The intestinal mucosa has the highest cell multiplication and renovation rates of the body, which clearly.

Pathophysiology of the Intestinal Barrier

The intestinal immune system is formed by a complex group of structures and specialized cell types that play an important role in protecting the body against aggressions from the external environment. It is estimated that approximately 25% of the intestinal mucosa is formed by lymphoid tissue and that 70-80% of the immunosecretory cells are located in the intestine. The intestinal immune cells group is called gut-associated lymphoid tissue (GALT) and is formed by:

Peyer's Patches (PPs): They can be compared to lymph nodes and are located in the intestinal lumen. They are covered by specialized epithelial cells called "M" cells or macrophages, responsible for presenting the antigens. The PPs are the main site of antigen presentation, onset and expression of the mucosal immunity. Different zones can be seen: intrafollicular, formed mainly by T-lymphocytes, and dome, formed by T-lymphocytes, plasma cells and macrophages. The macrophages found in the PPs have surface markers for T-helper and T cytotoxic/suppressant lymphocytes (CD4 and CD8, respectively).

Lymphoid cells of the lamina propria: The T- and B-lymphocytes, plasma cells, macrophages and eosinophils are included in this group. Approximately 80% of the plasma cells produce IgA, 15% produce IgM and a small amount of IgE.

Intraepithelial lymphocytes: They are located inside the lamina propria, the ratio between lymphocytes and epithelial cells being 1:6. This figure is influenced by the antigens and organisms present in the intestinal lumen.

The selective permeability ability of the intestinal walls is directly related to its integrity. Severe situations as burns, polytraumas, acute pancreatitis and prolonged fasting can lead to loss of this function. The consequence will be passage and translocation of bacteria and bacterial products (endotoxins, exotoxins, cell wall fragments) from the intestinal lumen to other extra-intestinal territories, and is reflected by a reduction in nutrients absorption, lower immune response and secretion of immune substances. This process results in an increased intestinal permeability and in the systemic inflammatory response syndrome. Alterations in the intestinal barrier that result in increased permeability are mediated mainly by three factors: cellular hypoxia; tissue lesion induced by mediators as free radicals, nitric oxide and cytokines; toxic effect of some bacteria on the intestinal lumen. Ischemia and reperfusion episodes can be seen as the final result, as well as modifications in the blood flow in different intestinal areas.

The Role of the Intestine in Critical Patients

For a long time, the intestine of critical patients was considered as physiologically inactive and with little pathophysiological meaning, thus having a secondary role in the recovery processes. Different from what was thought, however, the gut has a very important role in the patient's recovery, having endocrine and immune functions and acting as a protective barrier, separating the external and internal body environments. Human and animal studies have demonstrated that severely ill patients that received some form of enteral nutritional support had lower infection rates than those who received only parenteral nutrition or were fasted. This can be associated with a rapid and severe atrophy of GALT, increasing the risk of bacterial translocation, probably due to gut undernutrition secondary to food deprivation, demonstrating the important immune role played by the intestine.

There are increasing evidences that the maintenance of residual lymphoid mass of the intestine preserves local and systemic immunity. Recent evidences suggest that the presence of nutrients in the gastrointestinal tract provides trophic signals in addition to direct nutrition to the enterocytes. The trophic signals increase mesenteric blood flow, and stimulate the release of digestive enzymes and enterohormones, which influence proliferation and differentiation of intestinal cells, and the rate of mucosal cell turnover. The presence of food in the lumen, for example, is related to higher production of cholecystin that increases the calcium available for the lymphocytes, acting as a multiplication cofactor. Other benefits associated with enteral nutrition include increase of intraluminal IgA, regulation of inflammatory mediators production and reduction of bacterial virulence, a consequence of lower adhesin expression.

The prolonged use of Parenteral Nutrition (PN) is associated with impaired B- and T-lymphocyte function, altered leukocyte chemotaxis, impaired phagocytosis, and impaired bacterial and fungal killing. Human clinical studies and experimental models of sepsis using the dog as the experimental animal have demonstrated that these immunologic consequences are translated into a higher risk of infection in patients receiving only PN. While PN is associated with impaired innate and acquired immunity, it is also associated with a more pronounced proinflammatory response compared with enteral nutrition. Human patients undergoing colorectal surgery had higher interleukin-6 and interleukin-8 serum concentrations when fed parenterally versus enterally. In a new study enrolling healthy human volunteers challenged with endotoxin after oral intake was withheld for seven days, the group receiving PN had higher circulating levels of tumor necrosis factor-alpha and C-reactive protein than those receiving enteral feeding in the previous week. An enhanced proinflammatory response in patients receiving PN may explain the increased mortality seen in some categories of patients fed parenterally versus enterally.


When started early and aggressively, enteral nutritional support is an important and effective procedure assisting the treatment of critically ill patients. Besides providing nutrients essential to maintain immunity, the wound healing ability and drugs metabolism, enteral nutrition modulates the acute phase inflammatory response, maintains the gastrointestinal function and favors the adequate metabolism of the animal during critical stages of different types of injuries.


1.  Barr J, Hecht M, Flavin EK, et al. Outcomes in critically ill patients before and after the implementation of an evidence-based nutritional management protocol. Clinical Investigations in Critical Care, v. 125, n. 4, p. 1446-1457, 2004.

2.  Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Critical Care Medicine, v. 27, n. 12, p. 2799-2805, 1999.

3.  Devey JJ, Crowe DT, Kirby R. Postsurgical nutritional support. Journal of American Veterinary Medical Association, v. 206, n. 11, p. 1673-1675, 1995.

4.  Donoghue S, Kronfeld DS. Feeding hospitalised dogs and cats In: Wills JM, Simpson KW. The Waltham book of clinical nutrition of dog & cat. New York: Pergamon, 1994. p. 25-37.

5.  Jolliet P, Pichard C, Biolo G, et al. Enteral nutrition in intensive care patients: a practical approach. Intensive Care Medicine, v. 24, n. 8, p. 848-859, 1998.

6.  Li J, Kudsk KA, Gocynsky B, et al. Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue. Journal of Trauma, v. 39, n. 1, p. 44-52, 1995.

7.  Macintire DK. Bacterial translocation: clinical implications and prevention. In: Bonagura JD. Kirks Current Veterinary Therapy--Small Animal Practice. 13. ed. Philadelphia: W. B. Saunders Company, 2000, p. 201-203.

8.  Pérez CS. Tratado de Nutrición Artificial. Grupo Aula Médica, S. A., Madrid, 1998, p. 57-59.

9.  Roediger WEW. The starved colon-diminished mucosal nutrition, diminished absorption, and colitis. Diseases of the Colon & Rectum, v. 33, n. 10, p. 858-862, 1990.

10. Shenkin A. Micronutrients. In: Rombeau JL, Rolandelli RH. Clinical nutrition: enteral and tube feeding. Philadelphia: Saunders, 1997. p. 96-111.

11. Simpson KW, Birnbaum N. Fluid and electrolyte disturbances in gastrointestinal and pancreatic diseases. In: Dibartola SP. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice. St. Louis: Saunders Elsevier, 2006. p. 420-436.

12. Windsor ACJ, Kanwar S, LI Agk, et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut, v. 42, n. 1, p. 431-435, 1998.


Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Márcio Antonio Brunetto, DVM, MS, PhD
Clinical Nutrition Service
Teaching Veterinary Hospital of the São Paulo State University
Jaboticabal, SP, Brazil

MAIN : Clinical Nutrition : Enteral Nutrition
Powered By VIN