Principal Research Interest
The effect route and type of nutrition and malnutrition on host defenses, mucosal immunity, and vascular inflammatory responses.
Dr. Kudsk conducts basic research studying the interactions between nutritional status and infectious risk in surgical and critically injured patients. His research program investigates the effect of route and type of nutrition on mucosal immunity in the intestinal and respiratory tracts.
The program is designed to integrate and translate laboratory discoveries into clinical testing and medical practice. The goal is to define the mechanisms related to impaired nutritional status that increase postoperative infectious and healing complications in patients who are severely injured, critically ill, or undergoing major elective surgical procedures.
The laboratory research focuses on differences in host defenses between enterally and parenterally fed animals, pursuing laboratory and clinical studies that demonstrate significant immunologic benefits when nutrients are delivered enterally compared to intravenously. After tracing many of these differences to the mucosal immune system, which constitutes 50% of the body’s total immunity, our work shows that the size and integrity of mucosal immunity rapidly deteriorates when animals are not fed via the gastrointestinal tract. Simultaneously, established immunologic protection of mucosal surfaces against viruses and bacteria is lost. This system also loses its ability to respond to new pathogenic challenges.
Previous work by our group demonstrated significant reductions in the molecules responsible for directing naïve immunocytes into and through the mucosal immune system for distribution throughout the body. The expression of controlling molecules are related to alterations in tissue and cellular cytokine levels necessary to maintain integrity. In addition, cytokine changes simultaneously influence changes in the vascular endothelium of the gastrointestinal tract. These changes prime neutrophils and augment deleterious inflammatory responses throughout the body to subsequent stresses. Since many patients require intravenous feeding to avoid progressive starvation, we have found that several substances, when administered exogenously, can prevent and reverse the defect in mucosal immunity associated with parenteral feeding. Specific nutrients such as glutamine or products of the enteric nervous system (neuropeptides) reverse many of the deleterious affects of IV feeding. Clinical studies with these molecules are currently being planned.
The most recent focus of the program is the role of specialized secreting epithelial cells, specifically goblet and Paneth cells, in the small intestine that are vital to maintenance of the mucosal barrier. Production and secretion of specialized products from these cell types protects the mucosa from bacterial attachment and inflammation. We recently demonstrated parenteral feeding reduces release of antimicrobial Paneth cell products and the addition of neuropeptides may prevent these changes.
The effects of malnutrition on postoperative outcome after major general surgical procedures continue to be addressed in clinical studies. Our future work will identify specific preoperative nutritional markers predictive of a high complication rate to allow study of the effect of preoperative nutrient manipulation on improving clinical outcome by reducing postoperative complications. Collaboration with the basic science community throughout UW along with our colleagues in the Dept of Surgery continue to be an integral part of this approach.