The ProbioticEscherichia coliNissle 1917 Reduces Pathogen Invasion and Modulates Cytokine Expression in Caco-2 Cells Infected with Crohn's Disease-AssociatedE. coliLF82

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ABSTRACT

Increased numbers of adherent invasive Escherichia coli(AIEC) have been found in Crohn's disease (CD) patients. In this report, we investigate the potential of the probiotic Escherichia coliNissle 1917 (EcN) to reduce features associated with AIEC pathogenicity in an already established infection with AIEC reference strain LF82.

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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 Baumgart, Belgin Dogan, Mark Rishniw … (2007)

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.

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CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.

Pierre Desreumaux, Anne-Lise Glasser, Antonio C L Campos … (2007)

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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Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn's disease.

M C García-Malea López, Margarita Medina, L. Gil … (2009)

Escherichia coli, particularly the adherent-invasive E. coli (AIEC) pathovar, has been increasingly implicated in the ethiopathogenesis of Crohn's disease (CD). We describe the richness, abundance, diversity, and pathogenic features of E. coli and AIEC strains that colonize the intestinal mucosa. Approximately 100 E. coli colonies per biopsy from 20 CD patients (18 biopsies from colon and 23 from ileum) and 28 healthy controls (C) (25, colon; 27, ileum) were isolated. Repetitive extragenic palindrome-polymerase chain reaction (Rep-PCR) and pulsed field gel electrophoresis (PFGE) were used to analyze the clonality of isolates. For AIEC identification, adhesion and invasion assays were performed over Intestine-407 cells, and the capacity to survive and replicate intracellularly was determined over macrophages J774. The serotypes, phylotypes, and genotypes (19 virulence genes) of strains were also investigated. Mucosa-associated E. coli richness (E. coli subtypes/patient: C = 2.0 +/- 1.0; CD = 2.1 +/- 1.3) and diversity (Shannon Index: H'(C): 2.1 +/- 0.6; H'(CD): 2.5 +/- 0.8) were similar between CD and C, but higher E. coli counts were characteristic of CD patients (P = 0.010), particularly those with Crohn's ileitis (P = 0.001). Host-specific pulsotypes shared virulence features of ExPEC at similar frequencies between CD and C, except for iucD, which was more prevalent in E. coli from controls (C: 75%, CD: 40%, P = 0.027). In contrast, greater AIEC prevalence (% subjects with AIEC: CD = 51.9%; C = 16.7%; P = 0.003), abundance (% AIEC/E. coli: CD = 3.8 +/- 5.0%; C = 1.5 +/- 3.8%; P = 0.039), and richness (number of AIEC subtypes: CD = 0.8 +/- 1.4; C = 0.2 +/- 0.4; P = 0.015) of E. coli strains belonging to the AIEC pathovar was observed for CD patients. AIEC subtypes showed a high variability of seropathotypes and pulsotypes, although the B2 phylogroup was the most prevalent (AIEC: 64%, non-AIEC: 38%, P = 0.044). New data about ecological parameters of AIEC reinforces the implication of AIEC in CD.

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Journal

Title: Applied and Environmental Microbiology

Abbreviated Title: Appl. Environ. Microbiol.

Publisher: American Society for Microbiology

ISSN (Print): 0099-2240

ISSN (Electronic): 1098-5336

Publication date Created: March 22 2011

Publication date Created: April 01 2011

Publication date (Print): April 01 2011

Publication date (Electronic): February 11 2011

Volume: 77

Issue: 7

Pages: 2541-2544

Article

DOI: 10.1128/AEM.01601-10

SO-VID: 5f2694fd-c84a-47c2-bc27-9b423a6b33f7

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The ProbioticEscherichia coliNissle 1917 Reduces Pathogen Invasion and Modulates Cytokine Expression in Caco-2 Cells Infected with Crohn's Disease-AssociatedE. coliLF82

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ABSTRACT

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Most cited references 11

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.

CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.

Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn's disease.

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