Overview

Abstract

This symposium entitled, "Bacterial Colonization of the Gut and the Use of Pre- and Probiotics" was organized by the Shanghai Children's Medical Center of the Second Shanghai Medical University in conjunction with the Combined Program in Pediatric Gastroenterology and Nutrition at Harvard Medical School to underscore a 10-year agreement between both medical centers to provide training of academic pediatricians from China in basic and translational research. The training program is supported by a training grant from the National Institute of Child Health and Development (NICHD)/Fogarty Center (1-U01A145441-01), and research projects are, in part, supported by a research grant from Wyeth Nutritionals International, Inc., (Philadelphia, PA, U.S.A.) The symposium, itself, was sponsored from an educational grant from Wyeth Nutritionals International, Inc. for which the the organizers are grateful. The topic for this initial Sino-American symposium represents an important area of research in pediatrics and a major research interest of the two organizing groups. Dr. W. Allan Walker, a pediatric gastroenterologist with a strong research interest in the development of host defense, introduces the topic of the symposium by considering the importance of pre- and probiotics in the development of intestinal host defense in the extrauterine environment. He reviews the effects of initial colonization of the gut on the development of the effector immune response to antigen stimulation. At birth, the gut's lymphoid tissue has the capacity to respond to microbial-food antigens. However, the initial colonization of the newborn gut with indigenous microflora provides the appropriate "adjuvant effect" to activate antibody production and T-cell activation. Furthermore, the nature of initial oral feedings (breast-milk vs. formula) helps to determine the nature of colonizing bacteria (lactobacilli and bifidobacteria vs. enterobacteria and Escherichia coli). In addition, specific nutrients such as nucleotides, omega-3 fatty acids, and lactoferrin can enhance the effects of indigenous flora on strengthening the mucosal barrier and minimizing inflammatory responses to pathologic bacteria colonization. Dr. David S. Newburg, a glycobiologist from Harvard Medical School, reviews the importance of oligosaccharides in human milk on the attachment of pathologic bacteria to glycoconjugates and glycolipids and proteins in the intestinal microvillus membrane. Oligosaccharides, a natural prebiotic, has an influence on the nature of colonizing bacteria. He notes that enterocyte cell surface glycoconjugates are pathogen receptors and help to influence pathologic colonization of the newborn gut. In contrast, soluble oligosaccharides in breast milk can attach to "adhesions" on pathogens and thereby block their interaction with the intestinal surface and reduce their colonization. He cites examples of breast milk protection by oligosaccharides for Campylobacter and rotaviral infection. These studies may help to identify additives to future infant formula. Dr. Michael S. Caplan, a neonatologist from North-western University with a strong research interest in necrotizing enterocolitis, and Dr. Tamas Jilling reviews the possible role of probiotics in the treatment of necrotizing enterocolitis. The immature human enteric surface has an immature glycosylation pattern favoring colonization with pathologic organisms. In the premature neonate, this process may contribute to the pathogenesis of necrotizing enterocolitis. If probiotics are introduced into the diet of the newborn at birth, their presence could block pathologic colonization and thereby reduce the incidence of necrotizing enterocolitis. The authors provide evidence in an experimental model for necrotizing enterocolitis that the use of probiotics (Lactobacillus GG) can prevent the upregulation of platelet-activating factor, an inflammatory cytokine and indicator of early necrotizing enterocolitis. Dr. Dingwei Dai, an investigator at the Shanghai Children's Medical Center and a research fellow in the Developmental Gastroenterology Laboratory of the Combined Program in Pediatric Gastroenterology and Nutrition at Harvard Medical School, and colleagues from the United States present exciting new data to support the notion that glycosylation of microvillus membrane lipids and protein through glycosyltransferase activity is developmentally regulated and that cortisone treatment of pregnant or newborn animals can activate the maturation of this process. They also provide preliminary evidence that glycosylation in the human fetus is also under developmental regulation. These observations help explain pathologic colonization of the human newborn and the potential for treatment of this process with growth factors such as cortisone. Finally, Dr. Jon A. Vanderhoof, a pediatric gastroenterologist from the University of Nebraska Medical Center, reviews the use of probiotics in the treatment inflammatory disorders in infants and children. He reviews clinical studies to suggest that Lactobacillus GG administered orally to children who have rotaviral infection reduces the severity and length of time of the clinical illness. He also reviews its use in the treatment of allergic dermatitis of children and its preliminary use in the treatment of inflammatory bowel disease. These presentations provide an excellent review of the current state of our knowledge of the role of nutrients in bacterial colonization in health and disease of infants and children.