Abnormal CEACAM6 expression in Crohn disease patients favors gut colonization and inflammation by Adherent-Invasive<i>E. coli</i>

Barnich, Nicolas; Darfeuille‐Michaud, Arlette

doi:10.4161/viru.1.4.11510

Cited by 39 publications

(35 citation statements)

References 13 publications

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“…Their adhesion to ileal mucosa requires overexpression of CEACAM6, occurring in response to inflammation 38 39. The ‘paradigm’ ileal AIEC LF82,2 is afaC negative,16 although other ileal isolates tested were found to be afaC positive.…”

Section: Discussionmentioning

confidence: 99%

Colonic mucosa-associated diffusely adherentafaC+ Escherichia coliexpressinglpfAandpksare increased in inflammatory bowel disease and colon cancer

Prorok-Hamon

Friswell

Alswied

et al. 2013

Gut

194

166

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ObjectiveColonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates.DesignA fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome).Results454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin.ConclusionsIBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.

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Section: Discussionmentioning

confidence: 99%

Colonic mucosa-associated diffusely adherentafaC+ Escherichia coliexpressinglpfAandpksare increased in inflammatory bowel disease and colon cancer

Prorok-Hamon

Friswell

Alswied

et al. 2013

Gut

194

166

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“…As the first epithelial structure with which enteric pathogens come into contact, the glycocalyx forms an important physical barrier. The glycocalyx provides a surface for the attachment of commensal bacteria and includes, for example, members of the CEACAM (carcino-embryonic antigen-associated cell adhesion molecules) family, including carcino-embryonic antigen (CEACAM5) itself and also CEACAM6, the receptor for adherent-invasive Escherichia coli that are prevalent within the ileal mucosa of Crohn's disease (CD) patients [6]. The rapid turnover and clearance of the glycocalyx are thought to help with removal of attached pathogens [7,8].…”

Section: Components Of the Normal Mucosal Barriermentioning

confidence: 99%

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Merga

Campbell

Rhodes

2014

Dig Dis

156

113

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The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a ‘dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the ‘anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier, it is likely that environmental factors may be even more important. Some may be subtle and indirect, e.g. the effects of stress on the mucosa barrier, whilst others may be more obvious, e.g. the effect of pathogen-related gastroenteritis, known often to act as trigger for IBD relapse. We have also been very interested in the potentially harmful effects of ingested detergents - either by contamination of cutlery by inadequate rinsing or via ingestion of processed foods containing permitted emulsifiers. In vitro and ex vivo studies show that even very small trace amounts of these surfactants can greatly increase bacterial translocation. Implications for therapy are not yet so obvious. We advise our IBD patients to avoid processed foods containing emulsifiers and to rinse their dishes well - whilst accepting that there is no direct evidence yet to support this. Therapies that aim to enhance the mucosal barrier have yet to come to market, but trials of enteric-delivered phosphatidylcholine in UC are promising. The faecal concentration of mucus-degrading bact...

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“…One prototype strain of AIEC designated LF82 has been characterized in detail and was shown to bind to the CEACAM6 receptor expressed on epithelial cells ( Barnich et al, 2007). Expression of CEACAM6 is increased in inflamed tissue, explaining the increased abundance of E. coli on the mucosal biopsies of IBD patients (DarfeuilleMichaud et al, 2004;Barnich and Darfeuille-Michaud, 2010). Unlike acquired infectious pathogens, the pathobionts appear to require additional factors to cause disease.…”

Section: Mechanisms Of Immunomodulation By Specific Members Of the Inmentioning

confidence: 97%

Gnotobiology and the Study of Complex Interactions between the Intestinal Microbiota, Probiotics, and the Host

Tlaskalová‐Hogenová¹,

Kverka²,

Verdú³

et al. 2015

Mucosal Immunology

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Abnormal CEACAM6 expression in Crohn disease patients favors gut colonization and inflammation by Adherent-InvasiveE. coli

Cited by 39 publications

References 13 publications

Colonic mucosa-associated diffusely adherentafaC+ Escherichia coliexpressinglpfAandpksare increased in inflammatory bowel disease and colon cancer

Colonic mucosa-associated diffusely adherentafaC+ Escherichia coliexpressinglpfAandpksare increased in inflammatory bowel disease and colon cancer

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Gnotobiology and the Study of Complex Interactions between the Intestinal Microbiota, Probiotics, and the Host

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