Original Article

Subject Category: Microbe-microbe and microbe-host interactions

The ISME Journal (2007) 1, 403–418; doi:10.1038/ismej.2007.52; published online 12 July 2007

Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum

Martin Baumgart1,6, Belgin Dogan1,6, Mark Rishniw1, Gil Weitzman2, Brian Bosworth2, Rhonda Yantiss2, Renato H Orsi3, Martin Wiedmann3, Patrick McDonough4, Sung Guk Kim4, Douglas Berg5, Ynte Schukken4, Ellen Scherl2 and Kenneth W Simpson1

  1. 1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
  2. 2Division of Gastroenterology and Hepatology, Jill Roberts Inflammatory Bowel Disease Center, Weill Cornell Medical College, Cornell University, New York, NY, USA
  3. 3Department of Food Sciences, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, USA
  4. 4Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA
  5. 5Department of Molecular Microbiology, School of Medicine, Washington University, St Louis, MO, USA

Correspondence: Dr KW Simpson, Department of Clinical Sciences, Cornell University, C2001 College of Veterinary Medicine, Ithaca, NY 14850, USA. E-mail: kws5@cornell.edu

6These authors contributed equally to this manuscript.

Received 6 March 2007; Revised 19 May 2007; Accepted 31 May 2007; Published online 12 July 2007.

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Abstract

Intestinal bacteria are implicated increasingly as a pivotal factor in the development of Crohn's disease, but the specific components of the complex polymicrobial enteric environment driving the inflammatory response are unresolved. This study addresses the role of the ileal mucosa-associated microflora in Crohn's disease. A combination of culture-independent analysis of bacterial diversity (16S rDNA library analysis, quantitative PCR and fluorescence in situ hybridization) and molecular characterization of cultured bacteria was used to examine the ileal mucosa-associated flora of patients with Crohn's disease involving the ileum (13), Crohn's disease restricted to the colon (CCD) (8) and healthy individuals (7). Analysis of 16S rDNA libraries constructed from ileal mucosa yielded nine clades that segregated according to their origin (P<0.0001). 16S rDNA libraries of ileitis mucosa were enriched in sequences for Escherichia coli (P<0.001), but relatively depleted in a subset of Clostridiales (P<0.05). PCR of mucosal DNA was negative for Mycobacterium avium subspecies paratuberculosis, Shigella and Listeria. The number of E. coli in situ correlated with the severity of ileal disease (rho 0.621, P<0.001) and invasive E. coli was restricted to inflamed mucosa. E. coli strains isolated from the ileum were predominantly novel in phylogeny, displayed pathogen-like behavior in vitro and harbored chromosomal and episomal elements similar to those described in extraintestinal pathogenic E. coli and pathogenic Enterobacteriaceae. These data establish that dysbiosis of the ileal mucosa-associated flora correlates with an ileal Crohn's disease (ICD) phenotype, and raise the possibility that a selective increase in a novel group of invasive E. coli is involved in the etiopathogenesis to Crohn's disease involving the ileum.

Keywords:

adherent and invasive E. coli, dysbiosis, genome subtraction, inflammatory bowel disease, 16S rDNA

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