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Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo

BACKGROUND AND OBJECTIVES: Interaction of bacteria with the immune system within the intestinal mucosa plays a key role in the pathogenesis of inflammatory bowel disease (IBD). The aim of the current study was to develop a fluorescein-aided confocal laser endomicroscopy (CLE) method to visualise int...

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Autores principales: Moussata, Driffa, Goetz, Martin, Gloeckner, Annabel, Kerner, Marcus, Campbell, Barry, Hoffman, Arthur, Biesterfeld, Stephan, Flourie, Bernard, Saurin, Jean-Christophe, Galle, Peter R, Neurath, Markus F, Watson, Alastair J M, Kiesslich, Ralf
Formato: Texto
Lenguaje:English
Publicado: BMJ Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002833/
https://www.ncbi.nlm.nih.gov/pubmed/20980342
http://dx.doi.org/10.1136/gut.2010.213264
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author Moussata, Driffa
Goetz, Martin
Gloeckner, Annabel
Kerner, Marcus
Campbell, Barry
Hoffman, Arthur
Biesterfeld, Stephan
Flourie, Bernard
Saurin, Jean-Christophe
Galle, Peter R
Neurath, Markus F
Watson, Alastair J M
Kiesslich, Ralf
author_facet Moussata, Driffa
Goetz, Martin
Gloeckner, Annabel
Kerner, Marcus
Campbell, Barry
Hoffman, Arthur
Biesterfeld, Stephan
Flourie, Bernard
Saurin, Jean-Christophe
Galle, Peter R
Neurath, Markus F
Watson, Alastair J M
Kiesslich, Ralf
author_sort Moussata, Driffa
collection PubMed
description BACKGROUND AND OBJECTIVES: Interaction of bacteria with the immune system within the intestinal mucosa plays a key role in the pathogenesis of inflammatory bowel disease (IBD). The aim of the current study was to develop a fluorescein-aided confocal laser endomicroscopy (CLE) method to visualise intramucosal enteric bacteria in vivo and to determine the involved mucosal area in the colon and ileum in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Initially, E coli strains expressing enhanced green fluorescent protein (pEGFP) were endomicroscopically imaged in mice. In addition, ex vivo and in vivo imaging of fluorescent human enteric bacteria was performed to specify the distinct endomicroscopic appearance of enteral bacteria. Targeted mucosal biopsies towards endomicroscopic identifiable intramucosal bacteria and negative mucosal areas were prospectively obtained during colonoscopy and correlated with bench-top fluorescence microscopy (FISH) to prove the endomicroscopic visualisation of intramucosal bacteria. Finally, a retrospective analysis as well as a prospective study was performed in patients with UC and CD to confirm the presence and distribution of intramucosal bacteria within the gut. RESULTS: Confocal endomicroscopy was able to identify intramucosal pEGFP E coli in mice and strains of enteric microflora in the mucosa of humans. Using FISH as the gold standard, evaluation of 21 patients showed that CLE had a sensitivity of 89% and specificity of 100% to identify intramucosal bacteria. In a retrospective study, 113 patients with CD and UC had intramucosal bacteria significantly more often than 50 control patients (66% vs 60% vs 14%, p<0.001). This result was confirmed in a prospective study in which 10 patients with CD and 10 with UC had a significantly wider distribution of involvement with intramucosal bacteria in the colon and terminal ileum compared with 10 controls (85.2% vs 75.9% vs 16.8%, p<0.0001). CONCLUSIONS: CLE is a new tool that can image intramucosal bacteria in vivo in patients with IBD. Intramucosal bacteria are found more frequently and with a wider distribution in patients with IBD than in patients with a normal intestine.
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spelling pubmed-30028332010-12-23 Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo Moussata, Driffa Goetz, Martin Gloeckner, Annabel Kerner, Marcus Campbell, Barry Hoffman, Arthur Biesterfeld, Stephan Flourie, Bernard Saurin, Jean-Christophe Galle, Peter R Neurath, Markus F Watson, Alastair J M Kiesslich, Ralf Gut Endoscopy BACKGROUND AND OBJECTIVES: Interaction of bacteria with the immune system within the intestinal mucosa plays a key role in the pathogenesis of inflammatory bowel disease (IBD). The aim of the current study was to develop a fluorescein-aided confocal laser endomicroscopy (CLE) method to visualise intramucosal enteric bacteria in vivo and to determine the involved mucosal area in the colon and ileum in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Initially, E coli strains expressing enhanced green fluorescent protein (pEGFP) were endomicroscopically imaged in mice. In addition, ex vivo and in vivo imaging of fluorescent human enteric bacteria was performed to specify the distinct endomicroscopic appearance of enteral bacteria. Targeted mucosal biopsies towards endomicroscopic identifiable intramucosal bacteria and negative mucosal areas were prospectively obtained during colonoscopy and correlated with bench-top fluorescence microscopy (FISH) to prove the endomicroscopic visualisation of intramucosal bacteria. Finally, a retrospective analysis as well as a prospective study was performed in patients with UC and CD to confirm the presence and distribution of intramucosal bacteria within the gut. RESULTS: Confocal endomicroscopy was able to identify intramucosal pEGFP E coli in mice and strains of enteric microflora in the mucosa of humans. Using FISH as the gold standard, evaluation of 21 patients showed that CLE had a sensitivity of 89% and specificity of 100% to identify intramucosal bacteria. In a retrospective study, 113 patients with CD and UC had intramucosal bacteria significantly more often than 50 control patients (66% vs 60% vs 14%, p<0.001). This result was confirmed in a prospective study in which 10 patients with CD and 10 with UC had a significantly wider distribution of involvement with intramucosal bacteria in the colon and terminal ileum compared with 10 controls (85.2% vs 75.9% vs 16.8%, p<0.0001). CONCLUSIONS: CLE is a new tool that can image intramucosal bacteria in vivo in patients with IBD. Intramucosal bacteria are found more frequently and with a wider distribution in patients with IBD than in patients with a normal intestine. BMJ Group 2010-10-27 2011-01 /pmc/articles/PMC3002833/ /pubmed/20980342 http://dx.doi.org/10.1136/gut.2010.213264 Text en © 2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.
spellingShingle Endoscopy
Moussata, Driffa
Goetz, Martin
Gloeckner, Annabel
Kerner, Marcus
Campbell, Barry
Hoffman, Arthur
Biesterfeld, Stephan
Flourie, Bernard
Saurin, Jean-Christophe
Galle, Peter R
Neurath, Markus F
Watson, Alastair J M
Kiesslich, Ralf
Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
title Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
title_full Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
title_fullStr Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
title_full_unstemmed Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
title_short Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
title_sort confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo
topic Endoscopy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002833/
https://www.ncbi.nlm.nih.gov/pubmed/20980342
http://dx.doi.org/10.1136/gut.2010.213264
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