title: Gene-environment interactions in inflammatory bowel disease pathogenesis.
abstract: OBJECTIVE
  Inflammatory bowel disease (IBD) has long been known to have genetic risk factors because of increased prevalence in the relatives of affected individuals. However, genome-wide association studies have only explained limited heritability in IBD. The observed globally rising incidence of IBD has implicated the role of environmental factors. The hidden unexplained heritability remains to be explored.
  
  
  RESULTS
  Recent aggregate evidence has highlighted the extent and nature of host genome-microbiome associations, a key next step in understanding the mechanisms of pathogenesis in IBD. An individual's gut microbiota is shaped not only by genetic but also by environmental factors like diet. Minimizing exposure of the intestinal lumen to selected food items has shown to prolong the remission state of IBD. Among a genetically susceptible host, the shift of gut microbiota (or 'dysbiosis') can lead to increasing the susceptibility to IBD. With the advances in high-throughput large-scale 'omics' technologies in combination with creative data mining and system biology-based network analyses, the complexity of biological functional networks behind the cause of IBD has become more approachable. Therefore, the hidden heritability in IBD has become more explainable, and can be attributable to the changing environmental factors, epigenetic modifications, and gene-host microbial ('in-vironmental') or gene-extrinsic environmental interactions.
  
  
  CONCLUSIONS
  This review discusses the perspectives of relevance to clinical translation with emphasis on gene-environment interactions. No doubt, the use of system-based approaches will lead to the development of alternative, and hopefully better, diagnostic, prognostic, and monitoring tools in the management of IBD.
authors.affiliation: aDepartment of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic bDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Wang
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Achkar
mesh_terms: D041981:Gastrointestinal Tract / Q000382:microbiology; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000382:microbiology; D064307:Microbiota / Q000502:physiology; D012107:Research Design; D012907:Smoking / Q000009:adverse effects