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 P.; Bermúdez‐Humarán, Luis G.; Sokol, Harry; Thomas, Muriel; Langella, Philippe

doi:10.1128/mbio.00300-15

Cited by 229 publications

(199 citation statements)

References 55 publications

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“…For Faecalibacterium prausnitzii (Sokol et al 2008;Miquel et al 2015), 802 distinct strains were detectable in the analyzed samples (Fig. 4A), with only six subjects harboring a strain relatively close (3% SNV rate) to one of the three current isolate genomes.…”

Section: Strain-level Microbial Genetics Strongly Correlate With Geogmentioning

confidence: 99%

Microbial strain-level population structure and genetic diversity from metagenomes

et al. 2017

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Among the human health conditions linked to microbial communities, phenotypes are often associated with only a subset of strains within causal microbial groups. Although it has been critical for decades in microbial physiology to characterize individual strains, this has been challenging when using culture-independent high-throughput metagenomics. We introduce StrainPhlAn, a novel metagenomic strain identification approach, and apply it to characterize the genetic structure of thousands of strains from more than 125 species in more than 1500 gut metagenomes drawn from populations spanning North and South American, European, Asian, and African countries. The method relies on per-sample dominant sequence variant reconstruction within species-specific marker genes. It identified primarily subject-specific strain variants (<5% inter-subject strain sharing), and we determined that a single strain typically dominated each species and was retained over time (for >70% of species). Microbial population structure was correlated in several distinct ways with the geographic structure of the host population. In some cases, discrete subspecies (e.g., for Eubacterium rectale and Prevotella copri) or continuous microbial genetic variations (e.g., for Faecalibacterium prausnitzii) were associated with geographically distinct human populations, whereas few strains occurred in multiple unrelated cohorts. We further estimated the genetic variability of gut microbes, with Bacteroides species appearing remarkably consistent (0.45% median number of nucleotide variants between strains), whereas P. copri was among the most plastic gut colonizers. We thus characterize here the population genetics of previously inaccessible intestinal microbes, providing a comprehensive strain-level genetic overview of the gut microbial diversity.

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Section: Strain-level Microbial Genetics Strongly Correlate With Geogmentioning

confidence: 99%

Microbial strain-level population structure and genetic diversity from metagenomes

et al. 2017

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“…19 One month after the stable implantation of the two strains, mice were intrarectally inoculated with 2,4,6-TNBS (50 mg/kg body weight) to induce acute colitis, or with the vehicle (0.9% NaCl-ethanol) to obtain control mice. 20 Inflammation was monitored 48 h after TNBS administration. 250 mL of phenol pH4,8/chloroform-isoamyl alcohol (5:1) (Sigma) was added to caecum contents and the mix was agitated strongly.…”

Section: Mam Detection From Dixenic Micementioning

confidence: 99%

Identification of an anti-inflammatory protein fromFaecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease

Quévrain

Maubert

Michon

et al. 2015

Gut

620

460

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Background Crohn's disease (CD) associated dysbiosis is characterized 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 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 nonpolar residues. This last feature prevented the direct characterization 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 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. Conclusion A 15kDa 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.

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“…Commensal bacteria through their fermentation end products can therefore contribute to protective function. It is noteworthy that Faecalibacterium prausnitzii, a butyrate producing bacteria from Clostridium leptum group, is deficient in intestinal bowel disease (IBD) patients characterized by chronic intestinal inflammation [47], although this intriguing commensal is producing a lot of other metabolites with potential protective activities [48 ].…”

Section: Immune Response Is Shaped By Gut Microbiota and Conditioned mentioning

confidence: 99%

Metagenomics of the human intestinal tract: from who is there to what is done there

Cultrone

Tap²,

Lapaque

et al. 2015

Current Opinion in Food Science

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The human gastro-intestinal tract is colonized by 10 6 -10 14 microorganisms from the three domains, eukaria, archaea and bacteria that are collectively referred as the human gut microbiota. Gut microbiota actively contributes to the digestion of the nutrients, mainly the fibers otherwise undigested by the host, and participate to the host capacity of energy recovery from food. It plays also a key role in gut homeostasis, impacting on its barrier function and regulating the immune and metabolic systems. The target of this review is the diet-microbiota-host immune response triad. Starting from the current knowledge based on intestinal metagenomics, we point out on the role of food in shaping gut microbiota composition and functions, which is therefore mirrored in its healthful or deleterious effect on host immune response. Addresses

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Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii

Cited by 229 publications

References 55 publications

Microbial strain-level population structure and genetic diversity from metagenomes

Microbial strain-level population structure and genetic diversity from metagenomes

Identification of an anti-inflammatory protein fromFaecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease

Metagenomics of the human intestinal tract: from who is there to what is done there

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