title: Crohn's Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies.
abstract: Crohn's disease (CD) is a chronic, systemic, immune-mediated inflammation of the gastrointestinal tract. Originally described in 1932 as non-caseating granulomatous inflammation limited to the terminal ileum, it is now recognized as an expanding group of heterogeneous diseases defined by intestinal location, extent, behavior, and systemic extraintestinal manifestations. Joint diseases, including inflammatory spondyloarthritis and ankylosing spondylitis, are the most common extraintestinal manifestations of CD and share more genetic susceptibility loci than any other inflammatory bowel disease (IBD) trait. The high frequency and overlap with genes associated with infectious diseases, specifically Mendelian susceptibility to mycobacterial diseases (MSMD), suggest that CD may represent an evolutionary adaptation to environmental microbes. Elucidating the diversity of the enteric microbiota and the protean mucosal immune responses in individuals may personalize microbiome-targeted therapies and molecular classifications of CD. This review will focus on CD's natural history and therapies in the context of epigenetics, immunogenetics, and the microbiome.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02120, USA. emdefilippis@partners.org.
authors.forename: Ersilia M
authors.initials: EM
authors.lastname: DeFilippis
authors.affiliation: Jill Roberts Center for Inflammatory Bowel Disease, Jill Roberts Institute for Research in Inflammatory Bowel Disease, New York Presbyterian Hospital-Weill Cornell Medical College, 1315 York Avenue, Mezzanine Level, New York, NY, 10065, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Longman
authors.affiliation: New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Harbus
authors.affiliation: Weill Cornell Medical College, 1300 York Avenue, New York, NY, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Dannenberg
authors.affiliation: Jill Roberts Center for Inflammatory Bowel Disease, New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY, 1315 York Avenue, Mezzanine Level, New York, NY, 10065, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Scherl
mesh_terms: D001688:Biological Products / Q000627:therapeutic use; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000628:therapy*; D057890:Epigenomics / Q000379:methods*; D019143:Evolution, Molecular; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods; D057285:Precision Medicine / Q000379:methods
chemical_list: D001688:Biological Products
keywords: Environmental enteropathy; Epigenetics; Inflammatory bowel disease; Microbiome; Personalized medicine; Public health