title: Epigenetics and the developmental origins of inflammatory bowel diseases.
abstract: The gut microbiota, the intestinal mucosa and the host immune system are among the large biological networks involved in the development of inflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC). Host genetics and environmental factors can significantly modulate the interactive relationships among these biological systems and influence predilection toward IBD. High monozygotic twin discordance rates and the rapid rise in the prevalence of IBD indicate that environmental influences may be as important or even more important in their pathogenesis than genetic susceptibility. However, the nature and timing of environmental factors critical for inducing IBD remain largely unknown. The molecular mechanisms and the key biological component(s) that may be affected by such factors are also in question. Epigenetic changes, such as DNA methylation (the methylation of cytosines followed by a guanine in CpG dinucleotides) can be modified by environmental influences during finite developmental periods and have been implicated in the pathogenesis of IBD. Mucosal DNA methylation can also react to changes in the commensal microbiota, underscoring the intercalating relationships among the large biological systems involved in gastrointestinal disorders. Therefore, transient environmental influences during specific periods of development may induce critical change(s) in an isolated or concomitant fashion within the intestinal biomic networks and lead to increased susceptibility to IBD. The present review focuses on the emerging paradigm shift considering IBD to originate from critical environmental effects during pre- and postnatal development.
authors.affiliation: Department of Pediatrics, Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children's Hospital, USDA/ARS Children's Nutrition Research Center, Houston, Texas 77030-2399, USA. kellerma@bcm.edu
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
mesh_terms: D017668:Age of Onset; D019175:DNA Methylation; D004781:Environmental Exposure; D057890:Epigenomics; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D054892:Metagenome; D046188:Protein Modification, Translational
chemical_list: D006657:Histones