Gastroenterology

Gastroenterology

Volume 127, Issue 1, July 2004, Pages 80-93
Gastroenterology

Clinical-alimentary tract
Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer 1 ,

https://doi.org/10.1053/j.gastro.2004.03.054Get rights and content

Abstract

Background & Aims: Altered mucosal glycosylation in inflammatory bowel disease and colon cancer could affect mucosal bacterial adherence. This study aimed to quantify and characterize mucosa-associated and intramucosal bacteria, particularly Escherichia coli, in these conditions. Methods: Mucosa-associated bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples obtained at colonoscopy (Crohn’s disease, n = 14 patients; ulcerative colitis, n = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramucosal bacteria were grown after gentamicin treatment followed by hypotonic lysis. Results: Mucosa-associated and intramucosal bacteria were cultured more commonly in Crohn’s disease (79%, P = 0.03; and 71%, P < 0.01, respectively), but not ulcerative colitis (38% and 48%), than in noninflamed controls (42% and 29%) and were commonly cultured from colon cancers (71% and 57%). Mucosa-associated E. coli, which accounted for 53% of isolates, were more common in Crohn’s disease (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramucosal E. coli: Crohn’s disease, 29%; controls, 9%. E. coli expressed hemagglutinins in 39% of Crohn’s cases and 38% of cancers but only 4% of controls, and this correlated (P = 0.01) with adherence to the I407 and HT29 cell lines. Invasion was cell-line dependent. E. coli, including nonadherent isolates, induced interleukin-8 release from the cell lines. E. coli adhesins showed no blood group specificity, excepting 1 cancer isolate (HM44) with specificity for the Thomsen-Friedenreich antigen, but they could be blocked by soluble plantain fiber. Conclusions: These studies support a central role for mucosally adherent bacteria in the pathogenesis of Crohn’s disease and colon cancer. Soluble plant fibers that inhibit their adherence have therapeutic potential.

Section snippets

Patients

Eighty patients were studied: 21 with ulcerative colitis, 14 with Crohn’s disease, 21 with colon cancer, and 24 control patients, including irritable bowel syndrome (n = 13), sporadic polyposis (n = 4), piles (n = 3), diverticulitis (n = 2), pruritus ani (n = 1), and healthy (screening; n = 1). Biopsy samples were taken from the sigmoid colon by using standard endoscopic forceps during colonoscopy or flexible sigmoidoscopy for the inflammatory bowel disease and control patients and at resection

Mucosa-associated bacteria in Crohn’s disease and colon cancer

No significant difference was found in the number of bacteria present in the mucus layer (mucus-associated bacteria) cultured from inflammatory bowel disease patients compared with controls (Figure 1A). However, after the overlying mucus layer had been removed by dithiothreitol treatment, substantially more bacterial isolates were obtained from the mucosa (mucosa-associated bacteria) in Crohn’s disease (1201 colonies grown from 11/14 [79%] cases) compared with ulcerative colitis (1184 colonies

Discussion

This study demonstrates that, when the overlying mucus layer is removed, the normal colonic mucosa is relatively free from aerobic bacteria, whereas Crohn’s disease mucosae, the surface of colon cancers, and the distant mucosae from colon cancer resection specimens contain relatively plentiful aerobic flora, particularly E. coli. A high proportion of these E. coli express hemagglutinins and adhere to intestinal epithelial cell lines.

Previous studies of adherent E. coli in inflammatory bowel

References (53)

  • S.M. Henry

    Molecular diversity in the biosynthesis of GI tract glycoconjugates. A blood-group-related chart of microorganism receptors

    Transfus Clin Biol

    (2001)
  • S. Ryder et al.

    Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon cancer

    Gastroenterology

    (1994)
  • S.D. Ryder et al.

    Peanut ingestion increases rectal proliferation in individuals with mucosal expression of peanut lectin receptor

    Gastroenterology

    (1998)
  • J.M. Rhodes

    Unifying hypothesis for inflammatory bowel disease and associated colon cancersticking the pieces together with sugar

    Lancet

    (1996)
  • T. Hisamatsu et al.

    CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells

    Gastroenterology

    (2003)
  • R. Couper et al.

    Neutrophil dysfunction in glycogen storage disease Ibassociation with Crohn’s-like colitis

    Gastroenterology

    (1991)
  • J.J. Cebra

    Influences of microbiota on intestinal immune system development

    Am J Clin Nutr

    (1999)
  • M. Rhen et al.

    Organization of genes expressing the blood-group-M-specific haemagglutinin of Escherichia coliidentification and nucleotide sequence of the M-agglutinin subunit gene

    Gene

    (1986)
  • P. Karlen et al.

    Sialyl-Tn antigen as a marker of colon cancer risk in ulcerative colitisrelation to dysplasia and DNA aneuploidy

    Gastroenterology

    (1998)
  • G.H. Rabbani et al.

    Clinical studies in persistent diarrheadietary management with green banana or pectin in Bangladeshi children

    Gastroenterology

    (2001)
  • J. Boudeau et al.

    Invasive ability of an Escherichia coli strain isolated from the ileal mucosa of a patient with Crohn’s disease

    Infect Immun

    (1999)
  • A.L. Glasser et al.

    Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death

    Infect Immun

    (2001)
  • J.P. Hugot et al.

    Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease

    Nature

    (2001)
  • Y. Ogura et al.

    A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease

    Nature

    (2001)
  • M. O’Riordan et al.

    Innate recognition of bacteria by a macrophage cytosolic surveillance pathway

    Proc Natl Acad Sci U S A

    (2002)
  • M. Chamaillard et al.

    Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases

    Proc Natl Acad Sci U S A

    (2003)
  • Cited by (588)

    • Phytochemical analysis and biological evaluation of Ferulago setifolia K. Koch

      2024, Journal of the Science of Food and Agriculture
    • Pathogens in Crohn’s Disease: The Role of Adherent Invasive Escherichia coli

      2024, Critical Reviews in Eukaryotic Gene Expression
    View all citing articles on Scopus

    Supported by a research award from the National Association for Colitis and Crohn’s Disease (M/99/1) (to H.M.M.); research fellowships from the Digestive Diseases Foundation and the Medical Research Council (to C.M.); and Medical Research Council Co-operative grant GR990432.

    1

    The authors thank Professor T. K. Korhonen (Division of General Microbiology, University of Helsinki, Finland), who kindly donated Escherichia coli IH11165; Professor J.-F. Colombel (Laboratoire de Recherche sur les Maladies Inflammatoire de l’Intestine, Centre Hospitalier Universitaire, Lille, France) and Professor A. Darfeuille-Michaud (Faculte de Pharmacie, Clermont-Ferrand, France), who kindly donated the Crohn’s disease ileal isolates LF10 and LF82; and Dr. Keith Leiper (Gastroenterology Unit, Royal Liverpool & Broadgreen University Hospitals Trust, Liverpool, UK) for his cooperation in obtaining colorectal tissue specimens.

    As a consequence of the work described herein, a patent application has been filed by the University of Liverpool regarding the use of soluble plantain fiber in Crohn’s disease.

    View full text