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Gut. 2016 Mar;65(3):415-425. doi: 10.1136/gutjnl-2014-307649. Epub 2015 Jun 4.

Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease.

Quévrain E#1,2,3, Maubert MA#1,2,3,4, Michon C#5,6, Chain F5,6, Marquant R1,3,7, Tailhades J1,3,7, Miquel S5,6, Carlier L1,3,7, Bermúdez-Humarán LG5,6, Pigneur B1,2,3, Lequin O1,3,7, Kharrat P5,6, Thomas G1,2,3, Rainteau D1,2,3,4, Aubry C5,6, Breyner N5,6, Afonso C8, Lavielle S1,3,7, Grill JP1,2,3, Chassaing G1,3,7, Chatel JM5,6, Trugnan G1,2,3,4, Xavier R9, Langella P5,6, Sokol H#1,2,3,5,10, Seksik P#1,2,3,10.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, LBM, 27 rue de Chaligny, F-75012, Paris, France.
2
INSERM-ERL 1157 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine 27 rue de Chaligny, F-75012 Paris, France.
3
CNRS, UMR 7203 LBM, F-75005, Paris, France.
4
APHP, Hôpital Saint Antoine - Département PM2 Plateforme de Métabolomique, Peptidomique et dosage de Médicaments, F-75012 Paris, France.
5
INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France.
6
AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
7
Ecole Normale Supérieure- PSL Research University, Département de Chimie 24 rue Lhomond, F-75005 Paris, France.
8
Université de Rouen, UMR 6014 COBRA / IRCOF, F-76130 Mont Saint Aignan, France.
9
Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
10
APHP, Hôpital Saint Antoine - Service de Gastroentérologie et nutrition, F-75012 Paris, France.
#
Contributed equally

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.

KEYWORDS:

CELL BIOLOGY; CROHN'S DISEASE; IBD; INFLAMMATION; INTESTINAL BACTERIA

PMID:
26045134
PMCID:
PMC5136800
[Available on 2017-03-01]
DOI:
10.1136/gutjnl-2014-307649
[Indexed for MEDLINE]
Free PMC Article

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