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Gut. 2014 Oct;63(10):1566-77. doi: 10.1136/gutjnl-2012-303786. Epub 2014 Jan 16.

Bacterial protein signals are associated with Crohn's disease.

Author information

1
UMR1319 Micalis, INRA, Jouy-en-Josas, France.
2
Chair of Bioinformatics, Boku University Vienna, Vienna, Austria Department of Life Sciences, University of Warwick, Warwickshire, UK.
3
UMR1313 GABI, Iso Cell Express (ICE), INRA, Jouy-en-Josas, France.
4
Plate-forme d'Analyse Protéomique de Paris Sud-Ouest (PAPPSO), INRA, Gif-sur-Yvette, France.
5
Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC, Université de Strasbourg, Strasbourg, France.
6
Chair of Bioinformatics, Boku University Vienna, Vienna, Austria.
7
UMR1319 Micalis, INRA, Jouy-en-Josas, France Gastroenterology and Nutrition Unit, Hôpital Saint-Antoine, AP-HP, Paris, France.
8
UR1077, Mathématique Informatique et Génome (MIG), INRA, Jouy-en-Josas, France.
9
UR341, Mathématiques et Informatique Appliquées (MIA), INRA, Jouy-en-Josas, France.
10
Gastroenterology and Nutrition Unit, Hôpital Saint-Antoine, AP-HP, Paris, France.

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.

KEYWORDS:

Crohn's Disease; Enteric Bacterial Microflora; Inflammatory Bowel Disease

PMID:
24436141
PMCID:
PMC4173658
DOI:
10.1136/gutjnl-2012-303786
[Indexed for MEDLINE]
Free PMC Article
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