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Thirty years ago, responding to the growing interest, rapid expansion, and increase in research in pediatric gastroenterology and nutrition, we established the Journal of Pediatric Gastroenterology and Nutrition (JPGN). The editorial of the first edition began, quo vadis? (1). Thirty years later, we are asking the same question. What should the vision of JPGN be? It seems mandatory to provide the pediatric gastroenterologist with research and knowledge of gastrointestinal ontogenic function and malfunction during early life. It was hoped that the Journal would serve as an intellectual stimulus and an international forum for the presentation and discussion of advances and controversies within the discipline. The findings of differential timing of the expression of the genes controlling various small intestinal disaccharidases, pancreatic exocrine enzymes, and so on, led to a new practical paradigm on gut development (2). The paradigm included interaction of genetic endowment, gene expression, intrinsic biological clocks, endogenous regulatory mechanisms of the hypothalamic-hypophysial-thyroid-adrenal axis, gastrointestinal receptors and mediators, and environmental influences. The environmental influences affecting gut ontogeny included intrauterine growth retardation and malnutrition early in life (2). Barker (3) hypothesized that the effect of intrauterine growth retardation increases the risk of later-onset disease, particularly cardiovascular disease, hypertension, and type 2 diabetes mellitus in adults (3). The ontogeny of gut enzymes in early infancy and the recognition of pancreatic amylase deficiency and the early appearance of intestinal α-glucosidases and salivary amylase led to another ontogenic paradigm of alternate pathways of digestion and absorption in early infancy. The pragmatic outcome of ontogenic research was to use α-glucosides, such as sucrose, maltose, maltodextrins, and short polymers of glucose, during the neonatal period and for the compromised infant. Studies focused on the investigation and clinical applications of gastrointestinal ontogeny exemplify the early emphasis of JPGN. The potential for new therapeutic modalities attributable to age-related changes in the gut can stimulate clinical and basic research. The human genome project, the availability of stem cell biology, advances in molecular mechanisms of growth and development, and discoveries of mucosal growth factors and receptors that occurred as a result of the inception of JPGN have led to dramatic expansion of the basic, translational, and clinical studies in the Journal. We aspired to be one of the journals that publish original articles on gut ontogeny. In addition, we decided to invite ontogenic review articles that provided a basis for understanding the importance of gut ontogeny. Conversely, we were successful publishing age-related clinical studies in pediatric gastroenterology, with an emphasis on early life. An example of clinical disorders that we began to address successfully is celiac disease (CD). Clinical studies in CD emerged in the Journal, including global prevalence and high prevalence of silent preschool- and school-aged children, association with autoimmune disorders, Down syndrome, type 1 diabetes mellitus, and atypical presentations. Mechanistic studies of the effect of several genetic factors together with an environmental trigger were published. The genetic predisposition to CD was studied as a complex of HLA-DQA1*05/DQB1*02 and HLA-DQA*0301/DQB*0302 genes as major factors. Two strategies of genetic research—linkage and association studies—led to the discovery of several susceptibility loci and genes such as a region on 5q, MYO9B, and CTLA4. In addition, a genomewide association study identified 8 new risk regions, 7 of which harbour genes controlling the immune response. Again, we solicited review articles on genetic molecular biology research and the pathogenesis of CD. Another example for specific age-related clinical presentation and therapeutic considerations is failure to gain weight and short stature associated with pediatric inflammatory bowel disease (IBD). Pediatric IBD is different in some major aspects from adult IBD. Early-onset IBD has a distinct phenotype with disease manifestations that are primarily colonic with severe perianal disease and extragastrointestinal manifestations. Furthermore, early-onset IBD is unique in its association with metabolic diseases, neutrophil defects, immunodeficiency states, chronic granulomatous disease, and leukocyte adhesion defects. IBD is thought to result from a complex interplay of multiple genes and environmental factors. Large-scale genotyping techniques have resulted in identification of >30 IBD-associated genes. Pediatric IBD management must consider lifelong disease and treatment. Twenty-five percent of patients with IBD develop the disease in childhood and adolescence. Clinicians need to weigh the risks and benefits of selected therapies, particularly the effects of medications, such as steroids, on growth and development and lifetime of exposure. For the last 30 years, the Journal has published a significant number of articles addressing issues specifically focused on pediatric IBD. We realized that the greatest challenge facing JPGN was reaching out to the world in general and developing countries in particular. We solicited articles from developing countries and found worthwhile clinical observations, but we were challenged by the flaws of study design, such as inclusion and exclusion criteria, sample size, and statistical analyses; data presentation; results; and conclusions. We were confronted with English and grammatical mistakes, leading us to correct and rewrite articles, provided they had a sound scientific message for the pediatric gastroenterology community. A new dimension of the Journal was added when the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition started to develop and update clinical practice guidelines and recommendations (4,5). Overall, it is apparent that JPGN has evolved to become an important cornerstone for the discipline and a reference journal for the societies of pediatric gastroenterology, hepatology, and nutrition. My suggestion for the future is that the clinical research emphasizes acute and chronic gut diseases, all the while continuing to consider the effect of the ontogeny of the gut. In the quest to improve the knowledge of pediatric gastroenterology and nutrition, we should develop new areas of focus and analysis, perspectives, policy forums, and technical comments, similar to the journal Science. Presentation of the basic science news on the ontogeny of the gut, including cell biology, genetics, and immunology, should be a stimulus for inquiry and research to advance the frontiers of pediatric gastroenterology.
Emanuel Lebenthal (Wed,) studied this question.