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Crohn’s Disease May Be Differentiated Into 2 Distinct Biotypes Based on the Detection of Bacterial Genomic Sequences and Virulence Genes Within Submucosal Tissues

Chiodini, Rodrick J. PhD*; Dowd, Scot E. PhD; Davis, Brian MD; Galandiuk, Susan MD§; Chamberlin, William M. MD; Kuenstner, John Todd MD; McCallum, Richard W. MD#; Zhang, Jun PhD**,††

Journal of Clinical Gastroenterology: August 2013 - Volume 47 - Issue 7 - p 612–620
doi: 10.1097/MCG.0b013e31827b4f94
ALIMENTARY TRACT: Original Articles

Objective: To determine whether bacterial pathogens can be detected within the diseased submucosal tissues of patients with Crohn’s disease by molecular techniques independent of cultural methods.

Design: We designed a quantitative polymerase chain reaction to detect 32 virulence genes and transposons within submucosal tissues of patients with Crohn’s disease and controls and compared the microbiome of the submucosa with mucosal bacterial populations.

Results: Within submucosal tissues, the bacterial invasion/adherence genes eaeA and invA were detected in 43% of patients (P=0.01 and 0.008 vs. mucosa and controls, respectively) and the Mycobacterium-specific IS900 and 251F genes detected in 50% of patients (P=0.03 vs. mucosa and controls). These findings were mutually exclusive: invasion/adhesion genes and Mycobacterium-associated transposons were not detected in the same patient. Metagenomic sequencing and quantitative polymerase chain reaction results confirmed effective separation of the submucosal and mucosal microbiome and the existence of a submucosal bacterial population within diseased tissues.

Conclusions: This study is the first to examine the microbial populations of submucosal tissues during intestinal disease and provide evidence of a distinct submucosal microbiome and biotypes within Crohn’s disease. These data suggests that Crohn’s disease may not be a single disease, but a spectrum that can be divided into distinct biotypes based on the presence of invasion/adherence genes or Mycobacterium-associated transposons. If corroborated by larger population studies, these findings could revolutionize the diagnosis, management, and treatment of Crohn’s disease by the identification of patient biotypes and the application of targeted chemotherapeutic treatments that go beyond supportive in nature.

Supplemental Digital Content is available in the text.

*Division of Gastroenterology

#Division of Gastroenterology

**Department of Internal Medicine

††Department of Anesthesiology

Department of Surgery, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso

Molecular Research (Mr. DNA), Shallowater, TX

§Department of Surgery, University of Louisville, Louisville, KY

St. Vincent Physician Network, Sisters of Charity of Leavenworth Health System, Gastroenterology Associates, Billings, MT

Clinical Laboratories, Charleston Area Medical Center, Charleston, WV

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website,

Supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute Inc., and the Crohn’s Disease Initiative Inc.

Presented in part at American College of Gastroenterology Annual Scientific Meeting, Washington, DC, October 28 to November 2, 2011 and the Society for Surgery of the Alimentary Tract (SSAT), Digestive Disease Week (DDW), San Diego, CA, May 19 to 22, 2012.

The authors declare that they have nothing to disclose.

Reprints: Rodrick J. Chiodini, PhD, Department of Internal Medicine, Division of Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX 79905 (e-mail:

Received June 22, 2012

Accepted October 26, 2012

© 2013 by Lippincott Williams & Wilkins