Crohn’s Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies

  • Ersilia M. DeFilippisEmail author
  • Randy Longman
  • Michael Harbus
  • Kyle Dannenberg
  • Ellen J. Scherl
Small Intestine (D Sachar, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Small Intestine


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.


Microbiome Personalized medicine Inflammatory bowel disease Environmental enteropathy Epigenetics Public health 


Compliance with Ethical Standard

Conflicts of Interest

Ersilia M. DeFilippis, Randy Longman, Michael Harbus, and Kyle Dannenberg declare that they have no conflicts of interest. Ellen J. Scherl reports grants and research support from Abbott (AbbVie), AstraZeneca, CCFA, Elan, Janssen, Research & Development, JOMS Hopkins University, Mesoblast (formerly Osiris Therapeutics), Millennium Pharmaceuticals, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York CroM’s Foundation, Osiris Therapeutics, Pfizer, Prometheus Laboratories, Salix, UCB, and UCSF-CCFA Clinical Research Alliance; consultancy/advisory board membership with AbbVie, CroM’S and Colitis Foundation of America (CCFA), Entera Health, Evidera, 01 Health Foundation, Janssen, NPS Pharmaceutical, Prometheus, Protagonist Therapeutics, Salix, Seres Health, Shire, SUN FZE, Takeda Pharmaceuticals, and UCB; honoraria from OIHealth Foundation for non-branded speaker’s bureau, Janssen for non-branded speaker’s bureau, ClearView Healthcare Partners for market research; and a patent filed 16 February 2007, titled “E. coli and ileal Crohn’s disease: selective enrichment of ileal mucosa with E. coli of novel phylogeny.”

Human and Animal Rights and Informed Consent

With regard to the authors’ research cited in this paper, all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. In addition, all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ersilia M. DeFilippis
    • 1
    Email author
  • Randy Longman
    • 2
  • Michael Harbus
    • 3
  • Kyle Dannenberg
    • 4
  • Ellen J. Scherl
    • 5
  1. 1.Department of MedicineBrigham and Women’s HospitalBostonUSA
  2. 2.Jill Roberts Center for Inflammatory Bowel Disease, Jill Roberts Institute for Research in Inflammatory Bowel DiseaseNew York Presbyterian Hospital-Weill Cornell Medical CollegeNew YorkUSA
  3. 3.New York Institute of Technology College of Osteopathic MedicineNew YorkUSA
  4. 4.Weill Cornell Medical CollegeNew YorkUSA
  5. 5.Jill Roberts Center for Inflammatory Bowel DiseaseNew York Presbyterian Hospital-Weill Cornell Medical CollegeNew YorkUSA

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