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Article Dans Une Revue Gut Année : 2014

Bacterial protein signals are associated with Crohn's disease.

David P Kreil
  • Fonction : Auteur
Alain Guillot
  • Fonction : Auteur
Sebastian Vaca
  • Fonction : Auteur
Peter Sykacek
  • Fonction : Auteur
Florence Blon
  • Fonction : Auteur
Pascale Lepercq
  • Fonction : Auteur
  • PersonId : 1018610
Florence Levenez
  • Fonction : Auteur
Benoît Valot
Wilfrid Carré
  • Fonction : Auteur
  • PersonId : 834354
Valentin Loux
Nicolas Pons
  • Fonction : Auteur
Olivier David
Véronique Monnet

Résumé

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.

Domaines

Chimie organique
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Dates et versions

hal-00933734 , version 1 (28-05-2020)

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Catherine Juste, David P Kreil, Christian Beauvallet, Alain Guillot, Sebastian Vaca, et al.. Bacterial protein signals are associated with Crohn's disease.. Gut, 2014, 63 (10), pp.1566-1577. ⟨10.1136/gutjnl-2012-303786⟩. ⟨hal-00933734⟩
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