Are adherent Escherichia coli in Crohn’s disease and colon cancer truly pathogenic?

Abstract

The recent paper by Martin et al. made several interesting observations.1Martin H.M. Campbell B.J. Hart C.A. Mpofu C. Nayar M. Singh R. Englyst H. Williams H.F. Rhodes J.M. Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer.Gastroenterology. 2004; 127: 80-93Abstract Full Text Full Text PDF PubMed Scopus (537) Google Scholar However, the authors’ statement that their results “support a central role for mucosally adherent bacteria in the pathogenesis of Crohn’s disease and colon cancer” does not fulfill Koch’s postulates, even in the modern molecular era.2Falkow S. Molecular Koch’s postulates applied to bacterial pathogenicity–a personal recollection 15 years later.Nat Rev Microbiol. 2004; 2: 67-72Crossref PubMed Scopus (182) Google Scholar In particular, cause and effect for the inferred relationship between bacterial adhesion and mucosal disease is not established by the data presented. Several host and bacterial factors could have influenced the observed phenomena. For example, a whole range of enteric bacteria have been shown to adhere to fibronectin,3Froman G. Switalski L.M. Faris A. Wadstrom T. Hook M. Binding of Escherichia coli to fibronectin. A mechanism of tissue adherence.J Biol Chem. 1984; 259: 14899-14905PubMed Google Scholar type V collagen4Tarkkanen A.M. Allen B.L. Westerlund B. Holthofer H. Kuusela P. Risteli L. Clegg S. Korhonen T.K. Type V collagen as the target for type-3 fimbriae, enterobacterial adherence organelles.Mol Microbiol. 1990; 4: 1353-1361Crossref PubMed Scopus (74) Google Scholar and carcinoembryonic antigen,5Leusch H.G. Drzeniek Z. Markos-Pusztai Z. Wagener C. Binding of Escherichia coli and Salmonella strains to members of the carcinoembryonic antigen family differential binding inhibition by aromatic alpha-glycosides of mannose.Infect Immun. 1991; 59: 2051-2057Crossref PubMed Google Scholar each of which may be over-expressed by the mucosa in Crohn’s disease or colon cancer.6Greenstein A.J. Panvelliwalla D.K. Katz L.B. Heimann T.M. Donnelly J. Pertsimlidis D. Geller S. Smith H. Aufses Jr, A.H. Tissue carcinoembryonic antigen, dysplasia, and disease duration in colonic inflammatory bowel disease.Am J Gastroenterol. 1982; 77: 212-215PubMed Google Scholar, 7Graham M.F. Diegelmann R.F. Elson C.O. Lindblad W.J. Gotschalk N. Gay S. Gay R. Collagen content and types in the intestinal strictures of Crohn’s disease.Gastroenterology. 1988; 94: 257-265Abstract PubMed Google Scholar, 8Hanamura N. Yoshida T. Matsumoto E. Kawarada Y. Sakakura T. Expression of fibronectin and tenascin-C mRNA by myofibroblasts, vascular cells and epithelial cells in human colon adenomas and carcinomas.Int J Cancer. 1997; 73: 10-15ASCrossref PubMed Scopus (107) Google Scholar The finding that these bacteria subsequently adhered to cultured epithelial cells in vitro may reflect the activation of virulence genes induced by prior contact with the inflamed or neoplastic tissues. One might further speculate as to the effect of a magnesium-rich bowel preparation solution on bacterial genes regulated by the magnesium-sensitive phoP/phoQ regulatory system.9Groisman E.A. The pleiotropic two-component regulatory system PhoP-PhoQ.J Bacteriol. 2001; 183: 1835-1842Crossref PubMed Scopus (644) Google Scholar Finally, the authors’ demonstration of invasive, intracellular bacteria appeared to rest solely on the use of a gentamicin survival assay following lysis of epithelial cells. This would not exclude the possibility of adherent populations of gentamicin-resistant organisms and perhaps some supporting data from either confocal or electron microscopic studies would have been valuable. The recent report of an approximately 8-fold increase in the number of hospital isolates of gentamicin-resistant E. coli in the United Kingdom over the last decade would appear to support this more cautious interpretation.10Shannon K.P. French G.L. Increasing resistance to antimicrobial agents of Gram-negative organisms isolated at a London teaching hospital, 1995-2000.J Antimicrob Chemother. 2004; 53: 818-825Crossref PubMed Scopus (27) Google Scholar Although the manuscript by Martin et al. is intriguing, I would suggest there is still some way to go before we can describe either Crohn’s disease or colonic adenocarcinoma as “primarily a bacterial disease.” Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer GastroenterologyVol. 127Issue 1Preview 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. 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). Full-Text PDF ReplyGastroenterologyVol. 127Issue 5PreviewWe are grateful for Dr. Aspinall’s comments on our paper. We did not intend to imply that Koch’s postulates had been fulfilled by our report of increased numbers of mucosa-associated bacteria in Crohn’s disease and colon cancer. Indeed, it may be difficult to do this, given that there is probably a range of relevant mucosa-associated bacteria, with adhesive E. coli predominantly involved but not uniquely so. The various genetic animal models of inflammatory bowel disease have, however, all been shown to depend on the presence of nonpathogenic bacteria,1,2 and in one example, the IL-2 deficient mouse, E. Full-Text PDF