title: Mechanisms of Pediatric Inflammatory Bowel Disease.
abstract: Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, is characterized by chronic intestinal inflammation due to a complex interaction of genetic determinants, disruption of mucosal barriers, aberrant inflammatory signals, loss of tolerance, and environmental triggers. Importantly, the incidence of pediatric IBD is rising, particularly in children younger than 10 years. In this review, we discuss the clinical presentation of these patients and highlight environmental exposures that may affect disease risk, particularly among people with a background genetic risk. With regard to both children and adults, we review advancements in understanding the intestinal epithelium, the mucosal immune system, and the resident microbiota, describing how dysfunction at any level can lead to diseases like IBD. We conclude with future directions for applying advances in IBD genetics to better understand pathogenesis and develop therapeutics targeting key pathogenic nodes.
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease and.|Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114.|Harvard Medical School, Boston, Massachusetts 02115; email: joanna.peloquin@jhmi.edu , ggoel@ccib.mgh.harvard.edu , eduardo.villablanca@ki.se , xavier@molbio.mgh.harvard.edu.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Peloquin
authors.affiliation: Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114.|Harvard Medical School, Boston, Massachusetts 02115; email: joanna.peloquin@jhmi.edu , ggoel@ccib.mgh.harvard.edu , eduardo.villablanca@ki.se , xavier@molbio.mgh.harvard.edu.
authors.forename: Gautam
authors.initials: G
authors.lastname: Goel
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease and.|Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114.|Harvard Medical School, Boston, Massachusetts 02115; email: joanna.peloquin@jhmi.edu , ggoel@ccib.mgh.harvard.edu , eduardo.villablanca@ki.se , xavier@molbio.mgh.harvard.edu.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Villablanca
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease and.|Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114.|Harvard Medical School, Boston, Massachusetts 02115; email: joanna.peloquin@jhmi.edu , ggoel@ccib.mgh.harvard.edu , eduardo.villablanca@ki.se , xavier@molbio.mgh.harvard.edu.|Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142.|Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D064806:Dysbiosis / Q000276:immunology*; D004781:Environmental Exposure / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D007413:Intestinal Mucosa / Q000276:immunology*; D058990:Molecular Targeted Therapy
keywords: Crohn disease; genetics; intestinal homeostasis; microbiome; therapeutics; ulcerative colitis