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Original article
Bacterial protein signals are associated with Crohn’s disease
  1. Catherine Juste1,
  2. David P Kreil2,3,
  3. Christian Beauvallet4,
  4. Alain Guillot5,
  5. Sebastian Vaca6,
  6. Christine Carapito6,
  7. Stanislas Mondot1,
  8. Peter Sykacek2,
  9. Harry Sokol1,7,
  10. Florence Blon1,
  11. Pascale Lepercq1,
  12. Florence Levenez1,
  13. Benoît Valot5,
  14. Wilfrid Carré8,
  15. Valentin Loux8,
  16. Nicolas Pons1,
  17. Olivier David9,
  18. Brigitte Schaeffer9,
  19. Patricia Lepage1,
  20. Patrice Martin4,
  21. Véronique Monnet1,
  22. Philippe Seksik7,
  23. Laurent Beaugerie7,
  24. S Dusko Ehrlich1,
  25. Jean-François Gibrat8,
  26. Alain Van Dorsselaer6,
  27. Joël Doré1
  1. 1UMR1319 Micalis, INRA, Jouy-en-Josas, France
  2. 2Chair of Bioinformatics, Boku University Vienna, Vienna, Austria
  3. 3Department of Life Sciences, University of Warwick, Warwickshire, UK
  4. 4UMR1313 GABI, Iso Cell Express (ICE), INRA, Jouy-en-Josas, France
  5. 5Plate-forme d'Analyse Protéomique de Paris Sud-Ouest (PAPPSO), INRA, Gif-sur-Yvette, France
  6. 6Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), IPHC, Université de Strasbourg, Strasbourg, France
  7. 7Gastroenterology and Nutrition Unit, Hôpital Saint-Antoine, AP-HP, Paris, France
  8. 8UR1077, Mathématique Informatique et Génome (MIG), INRA, Jouy-en-Josas, France
  9. 9UR341, Mathématiques et Informatique Appliquées (MIA), INRA, Jouy-en-Josas, France
  1. Correspondence to Dr Catherine Juste, Bâtiment 405, INRA Domaine de Vilvert, Jouy-en-Josas 78350, France; catherine.juste{at}jouy.inra.fr

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.

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

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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