Effect of Route of Nutrition

8. Effect of Route of Nutrition

In addition to the composition and amount of diet fed, the route of feeding (enteral or parenteral) affects innate and adaptive aspects of immunity (Kudsk, 2002). A lack of enteral stimulation leads to decreased intestinal and respiratory tract IgA production and established IgA-mediated antiviral and antibacterial immunity (Renegar et al., 2001a). Increased mucosal permeability and bacterial translocation of luminal bacteria to the mesenteric lymph nodes, liver, and spleen are seen with parenteral nutrition (Kudsk, 2003a). In healthy cats, parenteral nutrition (PN) administered for 2 weeks resulted in small intestinal villous atrophy and fusion, and increased numbers of inflammatory cells (Lippert et al., 1989). These changes are reversed when enteral feeding is reinstated.

A lack of luminal nutrients results in an increased expression of proinflammatory adhesion molecules, especially ICAM-1. A lack of enteral feeding leads to infiltration of lymphocytes into the lamina propria and is associated with trapping of lymphocytes there, which is rapidly reversed with feeding (Ikeda et al., 2003). In addition, neutrophils accumulate and are activated within the vasculature of the intestine during fasting (Kudsk, 2002; 2003b).

The increased number of primed neutrophils adhering to the microvasculature throughout the intestinal tract are able to contribute to oxidative and enzymatic tissue damage following activation. Fasting or PN significantly increases ICAM-1 expression within the intestine and liver 3 hours after reperfusion compared with enteral feeding. Fasting or PN results in decreases in IL-4 and IL- 10 that correlate with decreases in IgA and increases in ICAM-1. Lack of enteral feeding impairs the coordinated system of sensitization, distribution, and interaction of T and B cells important in the production of IgA, in the maintenance of normal gut cytokines, and in the regulation of endothelial inflammation. Thus the lack of luminal nutrients has been described as a "first hit", and increases the inflammatory response to a secondary insult in the GIT, but also the lungs, liver, and potentially other organs as well.

Perhaps the effect of enteral nutrition on intestinal integrity is best demonstrated in cases where there is a severe mucosal insult. In canine parvoviral enteritis, the early instigation of enteral nutrition decreases the time to normalization of demeanor, appetite, vomiting, and diarrhea (Mohr et al., 2003). In a model of methotrexate induced enteritis in cats, feeding a complex diet was superior to fasting or feeding a purified diet in normalizing clinical signs, maintaining intestinal integrity, and minimizing bacterial translocation (Marks et al., 1997;1999).

Intestinal immunity can have a profound negative or positive influence in the development of the systemic inflammatory response to severe trauma, surgery, or infection. In human trauma patients, enteral feeding decreases the incidence of pneumonia compared with total parenteral nutrition or starvation. Enteral nutrition increases secretory IgA production at all mucosal sites and lack of enteral stimulation significantly impairs the generation of IgA-mediated mucosal immunity, including immunity against upper respiratory tract vial infections, hastening elimination of virus (Renegar et al., 2001b; Johnson et al., 2003). This has importance to feline medicine, where recovery from calici or herpes viral upper respiratory infection may be delayed in the absence of adequate enteral nutrition.

Intestinal integrity is compromised in the absence of enteral nutrients, and is accompanied by an increased rate of bacterial translocation, and increased risk of sepsis. These changes are seen with either complete fasting, or with parenteral nutrition. Thus oral fasting primes an animal for an exaggerated response to any subsequent or concurrent inflammatory insult and increases the bacterial challenge from enterically derived organisms. On the other hand, provision of enteral nutrition is one of the most important mechanisms by which systemic inflammatory responses can be reduced, and septicemia can be avoided. Compared to parenteral nutrition, enteral nutrition is beneficial in human critical patients. Patients without pre-existing septic shock who received enteral nutrition had fewer episodes of severe sepsis or septic shock, and the length of stay in ICU was shorter compared with those given PN (Radrizzani et al., 2006). This effect is so significant that it has lead some authors to recommend that parenteral nutrition be abandoned in cases of critical illness when enteral nutrition can be administered, even at an initial low caloric content.

Conclusion

The interaction between nutrition and immunity is complex, bi-directional, and incompletely understood. Nutrition can modify immunity by enhancing, suppressing, or changing the nature of an immune response. Immunity can be affected by diet in utero, and at the time of mounting a response. Nutrients of importance in this regard include glutamine, arginine, PUFA, carotenoids, and genistein. Nutrients can act as fuel, precursors for mediators, antioxidants, modifiers of gene transcription, and inhibitors of cellular functions. Defects in almost any essential nutrient can impair immunity, but also nutrient excess in obesity. Whether either suppression or enhancement is good or bad depends upon the specific disease state, and the individual patient.

Immune responses alter nutritional status through changes in usage, impaired uptake, increased loss, and altered metabolism. Sustained severe immune responses result in cachexia that cannot be reversed with feeding alone. The metabolic changes associated with systemic inflammatory responses leads to insulin resistance and hyperglycemia, and forced feeding can increase morbidity and mortality. Tight glucose control appears to be more important than meeting the resting energy requirements of critically ill patients. For optimal mucosal and systemic immunity, enteral nutrition is preferred to parenteral nutrition.

Diseases in which immunosuppression may be beneficial include chronic inflammatory diseases such as IBD, osteoarthritis, and immune-mediated diseases. It is less clear in which states enhancement of immunity is beneficial. Until more information is available, nutritional support should focus primarily on preventing nutritional deficiencies whilst avoiding overfeeding, rather than on immunomodulation.