Disturbed Pediatric Gut Microbiome Maturation in the Developmental Origins of Subsequent Chronic Disease

Abstract

The microbiome is known to play an important role in the development and maintenance of human health. During early childhood the gut microbiome undergoes a rapid evolution, making this developmental window most susceptible to microbial manipulation and, therefore, most vulnerable to environmental stimuli. Such stimuli may induce persistent alterations (or dysbiosis) in microbiome and/or host physiology, thereby resulting in susceptibility to subsequent disease development. This phenomenon is frequently described as “the microbial developmental origins of disease.” In this topic of the month, we call attention to the microbial developmental origins of disease by examining the potential for childhood antibiotic exposures and appendectomy (ie, inducers of dysbiosis) to influence the pathogenesis of certain multifactorial, common diseases (eg, celiac disease, inflammatory bowel disease, obesity), especially those with increasing incidence worldwide. We conclude that fully appreciating the critical components in the microbial developmental origins of common chronic disorders is a major task ahead of pediatric gastroenterologists in the 21st century. Such information will be key in working to prevent numerous common and emerging disorders.

Evolution of a Pathogenic Microbiome

“…In conjunction with reduced immune suppression from commensal bacteria, pathobionts lead to dysregulation in T cell differentiation that promotes the release of proinflammatory cytokines [77]. The resulting inflammatory environment induces host tissue damage and predisposes to diseases including IBD, irritable bowel syndrome, colorectal cancer, and extraintestinal diseases such as obesity and diabetes [78][79][80]. Table 1 outlines examples of several pathobionts and their molecular mediators suggested to contribute to disease.…”