Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease
By E. Quévrain, M. Maubert, Christophe Michon, F. Chain, Rodrigue Marquant, J. Tailhades, S. Miquel, L. Carlier, L. Bermúdez-Humarán, B. Pigneur and 16 more. Gut, 2015
740 citations recorded by the source corpus.
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.
Subfields: Food Science, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d70bb592688f445ad13a40f2579a02c64906096a
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Food Science
In Genetics
In Molecular Biology
Citations in the corpus
- Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut (2016, background): “Bifidobacteria will initially cleave, by means of the key enzyme fructose 6-phosphate phosphoketolase, one mole of fructose 6-phosphate into one mole of erythrose 4-phosphate and one mole of acetyl-phosphate (Figure 2A).”
- The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Indeed, supplementing mice with Lactococcus lactis expressing the F. prausnitzii microbial anti-inflammatory molecule alleviated intestinal inflammation (Quévrain et al., 2016; Breyner et al., 2017).”
- Probiotics, gut microbiota, and their influence on host health and disease (2017, background): “Also, a 15 kDa protein secreted by Faecalibacterium prausnitzii is able to inhibit the NF- B pathway in intestinal epithelial cells and to prevent colitis in an animal model [65].”
- Formation of propionate and butyrate by the human colonic microbiota. (2017, background): “prausnitzii is depleted in inflammatory bowel disease patients, especially Crohn’s disease, and evidence that it has anti-inflammatory action has attracted interest in this species as a potential therapeutic (Quévrain et al., 2016).”