title: Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease.
abstract: BACKGROUND
  Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined.
  
  
  METHODS
  Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice.
  
  
  RESULTS
  The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice.
  
  
  CONCLUSIONS
  A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
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authors.lastname: Quévrain
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|APHP, Hôpital Saint Antoine - Département PM2 Plateforme de Métabolomique, Peptidomique et dosage de Médicaments, F-75012 Paris, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
authors.forename: O
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
authors.forename: G
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|APHP, Hôpital Saint Antoine - Département PM2 Plateforme de Métabolomique, Peptidomique et dosage de Médicaments, F-75012 Paris, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Université de Rouen, UMR 6014 COBRA / IRCOF, F-76130 Mont Saint Aignan, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.
authors.forename: J-P
authors.initials: JP
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|APHP, Hôpital Saint Antoine - Département PM2 Plateforme de Métabolomique, Peptidomique et dosage de Médicaments, F-75012 Paris, France.
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authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
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authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.|APHP, Hôpital Saint Antoine - Service de Gastroentérologie et nutrition, F-75012 Paris, France.
authors.forename: H
authors.initials: H
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authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.|INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.|CNRS, UMR 7203 LBM, F-75005, Paris, France.|APHP, Hôpital Saint Antoine - Service de Gastroentérologie et nutrition, F-75012 Paris, France.
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mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D000068016:Eubacteriales / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D003424:Crohn Disease / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D064806:Dysbiosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000893:Anti-Inflammatory Agents; D001426:Bacterial Proteins; D015415:Biomarkers; D016328:NF-kappa B
keywords: CELL BIOLOGY; CROHN'S DISEASE; IBD; INFLAMMATION; INTESTINAL BACTERIA