Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; Chain, Florian; Lenoir, Marion; Raguideau, Sébastien; Hudault, Sylvie; Bridonneau, Chantal; Northen, Trent; Bowen, Benjamin; Bermúdez-Humarán, Luis G.; Sokol, Harry; Thomas, Muriel; Langella, Philippe

doi:10.1128/mBio.00300-15

Title: Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

Journal Article · Tue Apr 21 00:00:00 EDT 2015 · mBio (Online)

DOI:https://doi.org/10.1128/mBio.00300-15· OSTI ID:1215663

Miquel, Sylvie ^[1]; Leclerc, Marion ^[2]; Martin, Rebeca ^[1]; Chain, Florian ^[1]; Lenoir, Marion ^[1]; Raguideau, Sébastien ^[2]; Hudault, Sylvie ^[1]; Bridonneau, Chantal ^[1]; Northen, Trent ^[3]; Bowen, Benjamin ^[3]; Bermúdez-Humarán, Luis G. ^[1]; Sokol, Harry ^[4]; Thomas, Muriel ^[1]; Langella, Philippe ^[1]

Commensal and Probiotics-Host Interactions Lab., Jouy-en-Josas (France); AgroParisTech, Jouy-en-Josas (France)
AgroParisTech, Jouy-en-Josas (France); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Commensal and Probiotics-Host Interactions Lab., Jouy-en-Josas (France); AgroParisTech, Jouy-en-Josas (France); Univ. Pierre et Marie Curie (UPMC), Paris (France); Hopital Saint-Antoine, Assistance Publique-Hopitaux de Paris, Paris (France)

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1215663

Journal Information:: mBio (Online), Vol. 6, Issue 2; ISSN 2150-7511

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 164 works

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