In this first Sino-American Symposium, “Bacterial Colonization of the Gut and the Use of Pre-and Probiotics,” representative clinical and basic investigators have reviewed the importance of nutrients including functional foods (probiotics) in the initial colonization of the newborn gastrointestinal tract. In the introductory presentation, Dr. W. Allan Walker reviewed the importance of breast-feeding, the quintessential prebiotic, in establishing appropriate indigenous flora that are helpful in initiating mucosal host defenses, in accelerating the development of mucosal barrier function, and in establishing the symbiotic relationship between the host and its resident microflora. Dr. David S. Newburg reviewed the role of oligosaccharides as a prebiotic and as a potential inhibitor of pathologic colonization. He suggested that the oligosaccharides in human milk can specifically protect against known bacterial and viral pathogens causing neonatal infectious diarrhea. He concluded that a better understanding of the specific oligosaccharides may be helpful in establishing the rationale for their use as a food additive in infant formulas in the future.
In the next session, Drs. Michael S. Caplan and Tamas Jilling reviewed what is known about the pathogenesis of necrotizing enterocolitis and the role of pathologic colonization of the gut in its pathogenesis. They suggested that a combination of immature intestinal host defenses in premature infants and inappropriate bacterial-enterocyte “cross-talk” may be the pathophysiologic basis for the disease. They also suggested that inappropriate enteric feeding practices (e.g., introduction of infant formula rather than expressed human breast milk) may set the stage for this inappropriate microbial–epithelial interaction leading to excessive inflammatory cytokine production in the absence of neutralizing anti-inflammatory agents such as IL-10, TGF-α, and IL-1 receptor antagonist. They presented preliminary data to suggest that the use of probiotics in an animal model for necrotizing enterocolitis can prevent the expression of inflammatory cytokines and reduce the severity of disease. These preliminary animal studies provide a strong rationale for further clinical trials.
Dr. Dingwei Dai, a researcher from Shanghai working in the Developmental Gastroenterology Laboratory in the Combined Program in Pediatric Gastroenterology and Nutrition at Harvard, and colleagues present their basic research on the developmental regulation of glycosylation of lipids and proteins in the microvillus membrane in newborn rats and human fetuses. Glycosylation is regulated by the expression of glycosyltransferases. In the immature intestine of animals and human fetuses, sialotransferase is increased and fucosyl-and galactosyltransferases are decreased compared with their presence in the mature intestine. This immaturity may account for the trend toward pathologic colonization that occurs in premature small intestine, leading to necrotizing enterocolitis. Dai et al. also presented evidence that a known growth factor, cortisone, can accelerate the maturation of glycosyltransferases leading to colonization by appropriate indigenous flora. They provide preliminary evidence that neonatal colonization with nonpathologic flora (probiotics) can influence the expression of specific glycosyltransferases and may lead to increased protection against pathologic invasion leading to necrotizing enterocolitis.
Finally, Dr. Jon A. Vanderhoof reviewed his experience and the experience of other clinical investigators in using probiotics to prevent or treat gastrointestinal infectious conditions. He cited studies using Lactobacillus GG to treat nosocomial infections in patients in hospitals and chronic Clostridium difficile infection in patients receiving long-term antibiotic therapy. He also cited clinical evidence for the improvement of infants with allergic dermatitis and rotaviral gastroenteritis using probiotics. Finally, he suggested that inflammatory bowel disease, a chronic intestinal inflammatory condition due to excessive inflammatory cytokine responses to bacterial stimuli, may be modified or clinical exacerbations prevented by the chronic use of probiotics.
Thus, in this symposium, the experts on nutrition, bacterial colonization, and the use of prebiotics and probiotics have provided an excellent summary of the current state of our knowledge of this subject. These basic observations provide the basis for further clinical studies in the use of prebiotics and probiotics in the prevention or treatment gastrointestinal infection in children.