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      Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease

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          Abstract

          Background

          Inflammatory bowel disease (IBD) is used to describe a state of idiopathic, chronic inflammation of the gastrointestinal tract. The two main phenotypes of IBD are Crohn's disease (CD) and ulcerative colitis (UC). The major cause of IBD-associated mortality is colorectal cancer. Although both host-genetic and exogenous factors have been found to be involved, the aetiology of IBD is still not well understood. In this study we characterized thirteen Escherichia coli strains from patients with IBD by comparative genomic hybridization employing a microarray based on 31 sequenced E. coli genomes from a wide range of commensal and pathogenic isolates.

          Results

          The IBD isolates, obtained from patients with UC and CD, displayed remarkably heterogeneous genomic profiles with little or no evidence of group-specific determinants. No IBD-specific genes were evident when compared with the prototypic CD isolate, LF82, suggesting that the IBD-inducing effect of the strains is multifactorial. Several of the IBD isolates carried a number of extraintestinal pathogenic E. coli (ExPEC)-related virulence determinants such as the pap, sfa, cdt and hly genes. The isolates were also found to carry genes of ExPEC-associated genomic islands.

          Conclusions

          Combined, these data suggest that E. coli isolates obtained from UC and CD patients represents a heterogeneous population of strains, with genomic profiles that are indistinguishable to those of ExPEC isolates. Our findings indicate that IBD-induction from E. coli strains is multifactorial and that a range of gene products may be involved in triggering the disease.

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          Most cited references29

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          Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer.

          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). Intramucosal bacteria were grown after gentamicin treatment followed by hypotonic lysis. 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. 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.
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            CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.

            The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal epithelial cells. Here, we show that CD-associated AIEC strains adhere to the brush border of primary ileal enterocytes isolated from CD patients but not controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1 pili expression on the bacterial surface and on carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In addition, our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-gamma or TNF-alpha stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients.
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              Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis.

              Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non-pathogenic E. coli. A total of 120 patients with inactive ulcerative colitis were included in a double-blind, double-dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse-free times and global assessment. The start and end scores of the CAI demonstrated no significant difference (P = 0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse-free time of 103 +/- 4 days for mesalazine and 106 +/- 5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported. From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.
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                Author and article information

                Journal
                BMC Genomics
                BMC Genomics
                BioMed Central
                1471-2164
                2011
                15 June 2011
                : 12
                : 316
                Affiliations
                [1 ]Microbial Genomics and Antibiotic Resistance Group, DTU Food, Technical University of Denmark, DK-2800 Lyngby, Denmark
                [2 ]Department of Gastroenterology, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark
                [3 ]Department of Bacteriology, Mycology and Parasitology, Statens Serum Institut, DK-2300 Copenhagen S, Denmark
                Article
                1471-2164-12-316
                10.1186/1471-2164-12-316
                3155842
                21676223
                5ba73f2e-ef47-4acc-98f3-ce6ca35e7d7b
                Copyright ©2011 Vejborg et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 March 2011
                : 15 June 2011
                Categories
                Research Article

                Genetics
                escherichia coli,inflammatory bowel disease,lf82,urinary tract infections
                Genetics
                escherichia coli, inflammatory bowel disease, lf82, urinary tract infections

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