title: Crohn's disease may be differentiated into 2 distinct biotypes based on the detection of bacterial genomic sequences and virulence genes within submucosal tissues.
abstract: 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.
  
  
  METHODS
  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.
authors: Division of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA. rod@baystateservices.com
authors: Rodrick J
authors: RJ
authors: Chiodini
authors: Scot E
authors: SE
authors: Dowd
authors: Brian
authors: B
authors: Davis
authors: Susan
authors: S
authors: Galandiuk
authors: William M
authors: WM
authors: Chamberlin
authors: John Todd
authors: JT
authors: Kuenstner
authors: Richard W
authors: RW
authors: McCallum
authors: Jun
authors: J
authors: Zhang
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000328:Adult; D000368:Aged; D001419:Bacteria / Q000235:genetics / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003424:Crohn Disease / Q000145:classification / Q000382:microbiology*; D004269:DNA, Bacterial / Q000032:analysis*; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics; D005260:Female; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000235:genetics; D008875:Middle Aged; D009161:Mycobacterium / Q000235:genetics / Q000472:pathogenicity; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012475:Salmonella / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics; D015007:Yersinia / Q000235:genetics / Q000472:pathogenicity; D055815:Young Adult
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C073819:eaeA protein, E coli; C075518:invA protein, Bacteria