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Bacterial protein signals are associated with Crohn's disease
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(2014) Bacterial protein signals are associated with Crohn's disease. Gut, Volume 63 (Number 10). doi:10.1136/gutjnl-2012-303786 ISSN 0017-5749.
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Official URL: http://dx.doi.org/10.1136/gutjnl-2012-303786
Abstract
Objective No Crohn’s disease (CD) molecular maker has advanced to clinical use, and independent lines of evidence support a central role of the gut microbial community in CD. Here we explore the feasibility of extracting bacterial protein signals relevant to CD, by interrogating myriads of intestinal bacterial proteomes from a small number of patients and healthy controls.
Design We first developed and validated a workflow—including extraction of microbial communities, two-dimensional difference gel electrophoresis (2D-DIGE), and LC-MS/MS—to discover protein signals from CD-associated gut microbial communities. Then we used selected reaction monitoring (SRM) to confirm a set of candidates. In parallel, we used 16S rRNA gene sequencing for an integrated analysis of gut ecosystem structure and functions.
Results Our 2D-DIGE-based discovery approach revealed an imbalance of intestinal bacterial functions in CD. Many proteins, largely derived from Bacteroides species, were over-represented, while under-represented proteins were mostly from Firmicutes and some Prevotella members. Most overabundant proteins could be confirmed using SRM. They correspond to functions allowing opportunistic pathogens to colonise the mucus layers, breach the host barriers and invade the mucosae, which could still be aggravated by decreased host-derived pancreatic zymogen granule membrane protein GP2 in CD patients. Moreover, although the abundance of most protein groups reflected that of related bacterial populations, we found a specific independent regulation of bacteria-derived cell envelope proteins.
Conclusions This study provides the first evidence that quantifiable bacterial protein signals are associated with CD, which can have a profound impact on future molecular diagnosis.
Item Type: | Journal Article | ||||||||
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Subjects: | R Medicine > RC Internal medicine | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Science > Centre for Scientific Computing |
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Library of Congress Subject Headings (LCSH): | Crohn's disease, Gastrointestinal system -- Microbiology | ||||||||
Journal or Publication Title: | Gut | ||||||||
Publisher: | B M J Group | ||||||||
ISSN: | 0017-5749 | ||||||||
Official Date: | 16 January 2014 | ||||||||
Dates: |
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Volume: | Volume 63 | ||||||||
Number: | Number 10 | ||||||||
DOI: | 10.1136/gutjnl-2012-303786 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 26 December 2015 | ||||||||
Date of first compliant Open Access: | 26 December 2015 | ||||||||
Funder: | Wiener Wissenschafts, Forschungs und Technologiefonds [Vienna Science and Technology Fund] (WWTF), Baxter AG, Österreichisches Forschungszentrum Seibersdorf [Austrian Research Centre Seibersdorf] (ARCS), Austrian Center of Biopharmaceutical Technology (ACBT), Fondation pour la recherche médicale (FRM) | ||||||||
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