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Harry Sokol - One of the best experts on this subject based on the ideXlab platform.
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butyrate mediates anti inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through dact3
Gut microbes, 2020Co-Authors: Marion Lenoir, P. Langella, Florian Chain, Harry Sokol, Rebeca Martin, Edgar Torresmaravilla, Sead Chadi, Pamela Gonzalezdavila, Luis G BermudezhumaranAbstract:The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.
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Faecalibacterium prausnitzii skews human dc to prime il10 producing t cells through tlr2 6 jnk signaling and il 10 il 27 cd39 and ido 1 induction
Frontiers in Immunology, 2019Co-Authors: Joudy Alameddine, Chantal Bridonneau, Harry Sokol, Emmanuelle Godefroy, Loukas Papargyris, Guillaume Sarrabayrouse, Julie Tabiasco, Karina YazdanbakhshAbstract:The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases.
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Faecalibacterium prausnitzii Skews Human DC to Prime IL10-Producing T Cells Through TLR2/6/JNK Signaling and IL-10, IL-27, CD39, and IDO-1 Induction
'Frontiers Media SA', 2019Co-Authors: Joudy Alameddine, Chantal Bridonneau, Emmanuelle Godefroy, Loukas Papargyris, Guillaume Sarrabayrouse, Julie Tabiasco, Karina Yazdanbakhsh, Harry SokolAbstract:The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases
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phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes
Microbiome, 2018Co-Authors: Jeffrey K Cornuault, P. Langella, Harry Sokol, Marieagnes Petit, Mahendra Mariadassou, Leandro De Jesus Benevides, Elisabeth MoncautAbstract:Viral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. However, interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. In particular, no complete genomes of phages infecting F. prausnitzii are present in viral databases. We identified 18 prophages in 15 genomes of F. prausnitzii, used comparative genomics to define eight phage clades, and annotated the genome of the type phage of each clade. For two of the phages, we studied prophage induction in vitro and in vivo in mice. Finally, we aligned reads from already published viral metagenomic data onto the newly identified phages. We show that each phage clade represents a novel viral genus and that a surprisingly large fraction of them (10 of the 18 phages) codes for a diversity-generating retroelement, which could contribute to their adaptation to the digestive tract environment. We obtained either experimental or in silico evidence of activity for at least one member of each genus. In addition, four of these phages are either significantly more prevalent or more abundant in stools of IBD patients than in those of healthy controls. Since IBD patients generally have less F. prausnitzii in their microbiota than healthy controls, the higher prevalence or abundance of some of its phages may indicate that they are activated during disease. This in turn suggests that phages could trigger or aggravate F. prausnitzii depletion in patients. Our results show that prophage detection in sequenced strains of the microbiota can usefully complement viral metagenomic studies.
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the presence of the anti inflammatory protein mam from Faecalibacterium prausnitzii in the intestinal ecosystem
Gut, 2016Co-Authors: Harry Sokol, Elodie Quevrain, Marieanne Maubert, Bart Devreese, Philippe SeksikAbstract:We recently reported in your journal the discovery of an anti-inflammatory protein produced by Faecalibacterium prausnitzii , a commensal bacterium involved in Crohn's disease (CD) dysbiosis.1 We wish to highlight and complete these recent data. The involvement of the intestinal microbiota in the pathogenesis of CD is well recognised. It has been shown that dysbiosis (an imbalance in the composition of the intestinal microbiota) could participate in chronic and inappropriate activation of the intestinal immune system and lead to inflammation. Dysbiosis is characterised by a deficiency of certain bacteria, such …
P. Langella - One of the best experts on this subject based on the ideXlab platform.
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butyrate mediates anti inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through dact3
Gut microbes, 2020Co-Authors: Marion Lenoir, P. Langella, Florian Chain, Harry Sokol, Rebeca Martin, Edgar Torresmaravilla, Sead Chadi, Pamela Gonzalezdavila, Luis G BermudezhumaranAbstract:The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.
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phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes
Microbiome, 2018Co-Authors: Jeffrey K Cornuault, P. Langella, Harry Sokol, Marieagnes Petit, Mahendra Mariadassou, Leandro De Jesus Benevides, Elisabeth MoncautAbstract:Viral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. However, interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. In particular, no complete genomes of phages infecting F. prausnitzii are present in viral databases. We identified 18 prophages in 15 genomes of F. prausnitzii, used comparative genomics to define eight phage clades, and annotated the genome of the type phage of each clade. For two of the phages, we studied prophage induction in vitro and in vivo in mice. Finally, we aligned reads from already published viral metagenomic data onto the newly identified phages. We show that each phage clade represents a novel viral genus and that a surprisingly large fraction of them (10 of the 18 phages) codes for a diversity-generating retroelement, which could contribute to their adaptation to the digestive tract environment. We obtained either experimental or in silico evidence of activity for at least one member of each genus. In addition, four of these phages are either significantly more prevalent or more abundant in stools of IBD patients than in those of healthy controls. Since IBD patients generally have less F. prausnitzii in their microbiota than healthy controls, the higher prevalence or abundance of some of its phages may indicate that they are activated during disease. This in turn suggests that phages could trigger or aggravate F. prausnitzii depletion in patients. Our results show that prophage detection in sequenced strains of the microbiota can usefully complement viral metagenomic studies.
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Searching for the bacterial effector: The example of the multi-skilled commensal bacterium Faecalibacterium prausnitzii
Frontiers in Microbiology, 2018Co-Authors: Rebeca Martin, L. G. Bermúdez-humarán, P. LangellaAbstract:Faecalibacterium prausnitzii represents approximately 5% of the total fecal microbiota in healthy adults being one of the most abundant bacterium in the human intestinal microbiota of healthy adults. Furthermore, this bacterium has been proposed to be a sensor and a major actor of the human intestinal health because of its importance in the gut ecosystem. In this context, F. prausnitzii population levels have been found to be reduced in patients suffering from several syndromes and diseases such as inflammatory bowel diseases. These diseases are characterized by a breakage of the intestinal homeostasis called dysbiosis and the use of F. prausnitzii as a next generation probiotic (also called live biotherapeutics) has been proposed as a natural tool to restore such dysbiosis within the gut. Nevertheless, despite the potential importance of this bacterium in human health, little is known about its main effectors underlying its beneficial effects. In this perspective note, we aim to present the actual state in the research about F. prausnitzii effectors and the future milestones in this field.
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microbial anti inflammatory molecule mam from Faecalibacterium prausnitzii shows a protective effect on dnbs and dss induced colitis model in mice through inhibition of nf κb pathway
Frontiers in Microbiology, 2017Co-Authors: Natalia Martins Breyner, P. Langella, Florian Chain, C. Michon, Cassiana Sousa, Priscilla Vilas C B Boas, Vasco Azevedo, Jm ChatelAbstract:Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter. Moreover, we tested this protein on Dextran Sodium Sulfate (DSS)-induced colitis in mice. To study the effect of MAM we orally administered to the mice a Lactococcus lactis strain carrying a plasmid containing the cDNA of MAM under the control of a eukaryotic promoter. L. lactis delivered plasmids in epithelial cells of the intestinal membrane allowing thus the production of MAM directly by host. We showed that MAM administration inhibits NF-κB pathway in vivo. We confirmed the anti-inflammatory properties of MAM in DNBS-induced colitis but also in DSS model. In DSS model MAM was able to inhibit Th1 and Th17 immune response while in DNBS model MAM reduced Th1, Th2, and Th17 immune response and increased TGFβ production.
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Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses
Scientific Reports, 2016Co-Authors: Oriana Rossi, Hermie J. M. Harmsen, Harry J. Flint, Florian Chain, Harry Sokol, Sylvia H Duncan, Lisette A. Van Berkel, M. Tanweer Khan, Nico Taverne, P. LangellaAbstract:Faecalibacterium prausnitzii strain A2-165 was previously reported to have anti-inflammatory properties and prevent colitis in a TNBS model. We compared the immunomodulatory properties of strain A2-165 to four different F. prausnitzii isolates and eight abundant intestinal commensals using human dendritic cells (DCs) and mouse BMDCs in vitro. Principal component analysis revealed that the cytokine response to F. prausnitzii A2-165 is distinct from the other strains in eliciting high amounts of IL-10 secretion. The mouse DNBS model of relapsing IBD was used to compare the protective effects of F. prausnitzii A2-165 and Clostridium hathewayi, a low secretor of IL-10, on the Th1-driven inflammatory response to DNBS; attenuation of disease parameters was only observed with F. prausnitzii. In an in vivo mouse model of nasal tolerance to ovalbumin, F. prausnitzii A2-165 enhanced ovalbumin-specific T cell proliferation and reduced the proportion of IFN-γ+ T cells in CLNs. Similarly, in vitro F. prausnitzii A2-165 stimulated BMDCs increased ovalbumin-specific T cell proliferation and reduced the number of IFN-γ+ T cells. These mechanisms may contribute to the anti-inflammatory effects of F. prausnitzii in colitis and support the notion that this abundant bacterium might contribute to immune homeostasis in the intestine via its anti-inflammatory properties.
Sylvia H Duncan - One of the best experts on this subject based on the ideXlab platform.
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human gut Faecalibacterium prausnitzii deploys a highly efficient conserved system to cross feed on β mannan derived oligosaccharides
Mbio, 2021Co-Authors: Lars Jordhoy Lindstad, Leszek Michalak, Petra Louis, Shaun Leivers, Gabriel V Pereira, Asmund K Rohr, Eric C Martens, Lauren S Mckee, Sylvia H Duncan, Bjorge WesterengAbstract:β-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of β-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here, we show that a dominant butyrate producer in the human gut, Faecalibacterium prausnitzii, is able to acquire and degrade various β-mannooligosaccharides (β-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two β-MOS utilization loci (F. prausnitzii β-MOS utilization loci [FpMULs]) supported a concerted model whereby the imported β-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments of F. prausnitzii with the primary degraders Bacteroides ovatus and Roseburia intestinalis on polymeric β-mannan resulted in syntrophic growth, thus confirming the high efficiency of the FpMULs' uptake system. Genomic comparison with human F. prausnitzii strains and analyses of 2,441 public human metagenomes revealed that FpMULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of β-mannan metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut. IMPORTANCE Commensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic, and detailed biochemical analyses, this work reveals the mechanism enabling F. prausnitzii, as a model Ruminococcaceae within Firmicutes, to cross-feed and access β-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows that FpMULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of β-mannans/β-MOS as a common dietary component. Our findings provide a mechanistic understanding of the β-MOS utilization capability by F. prausnitzii that may be exploited to select dietary formulations specifically boosting this beneficial symbiont, and thus butyrate production, in the gut.
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human gut Faecalibacterium prausnitzii deploy a highly efficient conserved system to cross feed on β mannan derived oligosaccharides
bioRxiv, 2020Co-Authors: Lars Jordhoy Lindstad, Leszek Michalak, Shaun Leivers, Gabriel V Pereira, Asmund K Rohr, Eric C Martens, Lauren S Mckee, Bjorge Westereng, Sylvia H Duncan, Phillip B. PopeAbstract:{beta}-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of {beta}-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here we show that a dominant butyrate-producer in the human gut, Faecalibacterium prausnitzii, is able to acquire and degrade various {beta}-mannooligosaccharides ({beta}-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two {beta}-mannooligosaccharides ({beta}-MOS) utilization loci (FpMULs) supported a concerted model whereby the imported {beta}-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments of F. prausnitzii with the primary degrader Bacteroides ovatus on polymeric {beta}-mannan resulted in syntrophic growth and production of butyrate, thus confirming the high efficiency of the FpMULs uptake system. Genomic comparison with human F. prausnitzii strains and analyses of 2441 public human metagenomes revealed that FpMULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of {beta}-mannans metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut. ImportanceCommensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic and detailed biochemical analyses this work reveals the mechanism enabling F. prausnitzii, as a model clostridial cluster IV Firmicute, to cross-feed and access {beta}-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows that FpMULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of {beta}-mannans/{beta}-MOS as a common dietary component. Our findings provide a mechanistic understanding of the {beta}-MOS utilization capability by F. prausnitzii that may be exploited to select dietary formulations specifically boosting this beneficial symbiont, thus butyrate production, in the gut.
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alterations in the abundance and co occurrence of akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects
Frontiers in Cellular and Infection Microbiology, 2018Co-Authors: Mireia Lopezsiles, Jesus L Garciagil, Sylvia H Duncan, Xavier Aldeguer, Nuria Enrichcapo, Miriam Sabatmir, Margarita MartinezmedinaAbstract:Akkermansia muciniphila and Faecalibacterium prausnitzii, cohabitants in the intestinal mucosa, are considered members of a healthy microbiota and reduction of both species occurs in several intestinal disorders, including inflammatory bowel disease. Little is known however about a possible link between the reduction in quantity of these species, and in which circumstances this may occur. This study aims to determine the abundances and co-occurrence of the two species in order to elucidate conditions that may compromise their presence in the gut. Loads of A. muciniphila, total F. prausnitzii and its two phylogroup (16S rRNA gene copies) were determined by quantitative polymerase chain reaction in colonic biopsies from 17 healthy controls (H), 23 patients with ulcerative colitis (UC), 31 patients with Crohn's disease (CD), 3 with irritable bowel syndrome (IBS) and 3 with colorectal cancer (CRC). Data were normalized to total bacterial 16S rRNA gene copies in the same sample. Prevalence, relative abundances and correlation analyses were performed according to type of disease and considering relevant clinical characteristics of patients such as IBD location, age of disease onset, CD behavior, current medication and activity status. Co-occurrence of both species was found in 29% of H, 65% of UC and 29% of CD. Lower levels of total F. prausnitzii and phylogroups were found in subjects with CD, compared with H subjects (P ≤ 0.044). In contrast, no differences were found with the regard to A. muciniphila abundance across different disease states, but CD patients with disease onset below 16 years of age featured a marked depletion of this species. In CD patients, correlation between A. muciniphila and total F. prausnitzii (ρ = 0.362, P = 0.045) was observed, and particularly in those with non-stricturing, non-penetrating disease behavior and under moderate immunosuppressants therapy. Altogether, this study revealed that co-occurrence of both species differs between disease status. In addition, IBD patients featured a reduction of F. prausnitzii but similar loads of A. muciniphila when compared to H subjects, with the exception of those with early onset CD. Depletion of A. muciniphila in this subgroup of subjects suggests that it could be a potential biomarker to assist in pediatric CD diagnosis.
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Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics
The ISME Journal, 2017Co-Authors: Mireia Lopez-siles, L Jesús Garcia-gil, Sylvia H Duncan, Margarita Martinez-medinaAbstract:There is an increasing interest in Faecalibacterium prausnitzii , one of the most abundant bacterial species found in the gut, given its potentially important role in promoting gut health. Although some studies have phenotypically characterized strains of this species, it remains a challenge to determine which factors have a key role in maintaining the abundance of this bacterium in the gut. Besides, phylogenetic analysis has shown that at least two different F. prausnitzii phylogroups can be found within this species and their distribution is different between healthy subjects and patients with gut disorders. It also remains unknown whether or not there are other phylogroups within this species, and also if other Faecalibacterium species exist. Finally, many studies have shown that F. prausnitzii abundance is reduced in different intestinal disorders. It has been proposed that F. prausnitzii monitoring may therefore serve as biomarker to assist in gut diseases diagnostics. In this mini-review, we aim to serve as an overview of F. prausnitzii phylogeny, ecophysiology and diversity. In addition, strategies to modulate the abundance of F. prausnitzii in the gut as well as its application as a biomarker for diagnostics and prognostics of gut diseases are discussed. This species may be a useful potential biomarker to assist in ulcerative colitis and Crohn’s disease discrimination.
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Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses
Scientific Reports, 2016Co-Authors: Oriana Rossi, Hermie J. M. Harmsen, Harry J. Flint, Florian Chain, Harry Sokol, Sylvia H Duncan, Lisette A. Van Berkel, M. Tanweer Khan, Nico Taverne, P. LangellaAbstract:Faecalibacterium prausnitzii strain A2-165 was previously reported to have anti-inflammatory properties and prevent colitis in a TNBS model. We compared the immunomodulatory properties of strain A2-165 to four different F. prausnitzii isolates and eight abundant intestinal commensals using human dendritic cells (DCs) and mouse BMDCs in vitro. Principal component analysis revealed that the cytokine response to F. prausnitzii A2-165 is distinct from the other strains in eliciting high amounts of IL-10 secretion. The mouse DNBS model of relapsing IBD was used to compare the protective effects of F. prausnitzii A2-165 and Clostridium hathewayi, a low secretor of IL-10, on the Th1-driven inflammatory response to DNBS; attenuation of disease parameters was only observed with F. prausnitzii. In an in vivo mouse model of nasal tolerance to ovalbumin, F. prausnitzii A2-165 enhanced ovalbumin-specific T cell proliferation and reduced the proportion of IFN-γ+ T cells in CLNs. Similarly, in vitro F. prausnitzii A2-165 stimulated BMDCs increased ovalbumin-specific T cell proliferation and reduced the number of IFN-γ+ T cells. These mechanisms may contribute to the anti-inflammatory effects of F. prausnitzii in colitis and support the notion that this abundant bacterium might contribute to immune homeostasis in the intestine via its anti-inflammatory properties.
Chantal Bridonneau - One of the best experts on this subject based on the ideXlab platform.
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Faecalibacterium prausnitzii skews human dc to prime il10 producing t cells through tlr2 6 jnk signaling and il 10 il 27 cd39 and ido 1 induction
Frontiers in Immunology, 2019Co-Authors: Joudy Alameddine, Chantal Bridonneau, Harry Sokol, Emmanuelle Godefroy, Loukas Papargyris, Guillaume Sarrabayrouse, Julie Tabiasco, Karina YazdanbakhshAbstract:The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases.
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Faecalibacterium prausnitzii Skews Human DC to Prime IL10-Producing T Cells Through TLR2/6/JNK Signaling and IL-10, IL-27, CD39, and IDO-1 Induction
'Frontiers Media SA', 2019Co-Authors: Joudy Alameddine, Chantal Bridonneau, Emmanuelle Godefroy, Loukas Papargyris, Guillaume Sarrabayrouse, Julie Tabiasco, Karina Yazdanbakhsh, Harry SokolAbstract:The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases
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functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers a step forward in the use of f prausnitzii as a next generation probiotic
Frontiers in Microbiology, 2017Co-Authors: Rebeca Martin, Chantal Bridonneau, Véronique Robert, Sylvie Miquel, Florian Chain, Leandro De Jesus Benevides, Sylvie Hudault, Olivier BerteauAbstract:Faecalibacterium prausnitzii is a major member of the Firmicutes phylum and one of the most abundant bacteria in the healthy human microbiota. F. prausnitzii depletion has been reported in several intestinal disorders, and more consistently in Crohn’s disease (CD) patients. Despite its importance in human health, only few microbiological studies have been performed to isolate novel F. prausnitzii strains in order to better understand the biodiversity and physiological diversity of this beneficial commensal species. In this study, we described a protocol to isolate novel F. prausnitzii strains from feces of healthy volunteers as well as a deep molecular and metabolic characterization of these isolated strains. These F. prausnitzii strains were classified in two phylogroups and 3 clusters according to 16S rRNA sequences and results support that they would belong to two different genomospecies or genomovars as no genome sequencing has been performed in this work. Differences in enzymes production, antibiotic resistance and immunomodulatory properties were found to be strain-dependent. So far, all F. prausnitzii isolates share some characteristic such as i) the lack of epithelial cells adhesion, plasmids, anti-microbial and hemolytic activity and ii) the presence of DNAse activity. Furthermore, Short Chain Fatty Acids (SCFA) production was assessed for the novel isolates as these products influence intestinal homeostasis. Indeed, the butyrate production has been correlated to the capacity to induce IL-10, an anti-inflammatory cytokine, in peripheral blood mononuclear cells (PBMC) but not to the ability to block IL-8 secretion in TNF-α-stimulated HT-29 cells, reinforcing the hypothesis of a complex anti-inflammatory pathway driven by F. prausnitzii. Altogether, our results suggest that some F. prausnitzii strains could represent good candidates as next-generation probiotic.
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Ecology and metabolism of the beneficial intestinal commensal bacterium Faecalibacterium prausnitzii
Gut microbes, 2014Co-Authors: Sylvie Miquel, Chantal Bridonneau, Véronique Robert, Muriel Thomas, L. G. Bermúdez-humarán, Harry Sokol, Rebeca Martin, P. LangellaAbstract:Faecalibacterium prausnitzii is a major commensal bacterium, and its prevalence is often decreased in conditions of intestinal dysbiosis. The phylogenic identity of this bacterium was described only recently. It is still poorly characterized, and its specific growth requirements in the human gastrointestinal tract are not known. In this review, we consider F. prausnitzii metabolism, its ecophysiology in both humans and animals, and the effects of drugs and nutrition on its population. We list important questions about this beneficial and ubiquitous commensal bacterium that it would be valuable to answer.
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bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent
BMC Biology, 2013Co-Authors: Laura Wrzosek, Stephan Bouet, Marie Joncquel Chevaliercurt, Catherine Philippe, Marielouise Noordine, Véronique Robert, Sylvie Miquel, Chantal BridonneauAbstract:The intestinal mucus layer plays a key role in the maintenance of host-microbiota homeostasis. To document the crosstalk between the host and microbiota, we used gnotobiotic models to study the influence of two major commensal bacteria, Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii, on this intestinal mucus layer. B. thetaiotaomicron is known to use polysaccharides from mucus, but its effect on goblet cells has not been addressed so far. F. prausnitzii is of particular physiological importance because it can be considered as a sensor and a marker of human health. We determined whether B. thetaiotaomicron affected goblet cell differentiation, mucin synthesis and glycosylation in the colonic epithelium. We then investigated how F. prausnitzii influenced the colonic epithelial responses to B. thetaiotaomicron. B. thetaiotaomicron, an acetate producer, increased goblet cell differentiation, expression of mucus-related genes and the ratio of sialylated to sulfated mucins in mono-associated rats. B. thetaiotaomicron, therefore, stimulates the secretory lineage, favoring mucus production. When B. thetaiotaomicron was associated with F. prausnitzii, an acetate consumer and a butyrate producer, the effects on goblet cells and mucin glycosylation were diminished. F. prausnitzii, by attenuating the effects of B. thetaiotaomicron on mucus, may help the epithelium to maintain appropriate proportions of different cell types of the secretory lineage. Using a mucus-producing cell line, we showed that acetate up-regulated KLF4, a transcription factor involved in goblet cell differentiation. B. thetaiotaomicron and F. prausnitzii, which are metabolically complementary, modulate, in vivo, the intestinal mucus barrier by modifying goblet cells and mucin glycosylation. Our study reveals the importance of the balance between two main commensal bacteria in maintaining colonic epithelial homeostasis via their respective effects on mucus.
Rebeca Martin - One of the best experts on this subject based on the ideXlab platform.
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butyrate mediates anti inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through dact3
Gut microbes, 2020Co-Authors: Marion Lenoir, P. Langella, Florian Chain, Harry Sokol, Rebeca Martin, Edgar Torresmaravilla, Sead Chadi, Pamela Gonzalezdavila, Luis G BermudezhumaranAbstract:The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.
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Searching for the bacterial effector: The example of the multi-skilled commensal bacterium Faecalibacterium prausnitzii
Frontiers in Microbiology, 2018Co-Authors: Rebeca Martin, L. G. Bermúdez-humarán, P. LangellaAbstract:Faecalibacterium prausnitzii represents approximately 5% of the total fecal microbiota in healthy adults being one of the most abundant bacterium in the human intestinal microbiota of healthy adults. Furthermore, this bacterium has been proposed to be a sensor and a major actor of the human intestinal health because of its importance in the gut ecosystem. In this context, F. prausnitzii population levels have been found to be reduced in patients suffering from several syndromes and diseases such as inflammatory bowel diseases. These diseases are characterized by a breakage of the intestinal homeostasis called dysbiosis and the use of F. prausnitzii as a next generation probiotic (also called live biotherapeutics) has been proposed as a natural tool to restore such dysbiosis within the gut. Nevertheless, despite the potential importance of this bacterium in human health, little is known about its main effectors underlying its beneficial effects. In this perspective note, we aim to present the actual state in the research about F. prausnitzii effectors and the future milestones in this field.
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functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers a step forward in the use of f prausnitzii as a next generation probiotic
Frontiers in Microbiology, 2017Co-Authors: Rebeca Martin, Chantal Bridonneau, Véronique Robert, Sylvie Miquel, Florian Chain, Leandro De Jesus Benevides, Sylvie Hudault, Olivier BerteauAbstract:Faecalibacterium prausnitzii is a major member of the Firmicutes phylum and one of the most abundant bacteria in the healthy human microbiota. F. prausnitzii depletion has been reported in several intestinal disorders, and more consistently in Crohn’s disease (CD) patients. Despite its importance in human health, only few microbiological studies have been performed to isolate novel F. prausnitzii strains in order to better understand the biodiversity and physiological diversity of this beneficial commensal species. In this study, we described a protocol to isolate novel F. prausnitzii strains from feces of healthy volunteers as well as a deep molecular and metabolic characterization of these isolated strains. These F. prausnitzii strains were classified in two phylogroups and 3 clusters according to 16S rRNA sequences and results support that they would belong to two different genomospecies or genomovars as no genome sequencing has been performed in this work. Differences in enzymes production, antibiotic resistance and immunomodulatory properties were found to be strain-dependent. So far, all F. prausnitzii isolates share some characteristic such as i) the lack of epithelial cells adhesion, plasmids, anti-microbial and hemolytic activity and ii) the presence of DNAse activity. Furthermore, Short Chain Fatty Acids (SCFA) production was assessed for the novel isolates as these products influence intestinal homeostasis. Indeed, the butyrate production has been correlated to the capacity to induce IL-10, an anti-inflammatory cytokine, in peripheral blood mononuclear cells (PBMC) but not to the ability to block IL-8 secretion in TNF-α-stimulated HT-29 cells, reinforcing the hypothesis of a complex anti-inflammatory pathway driven by F. prausnitzii. Altogether, our results suggest that some F. prausnitzii strains could represent good candidates as next-generation probiotic.
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identification of metabolic signatures linked to anti inflammatory effects of Faecalibacterium prausnitzii
Mbio, 2015Co-Authors: Sylvie Miquel, Florian Chain, Rebeca Martin, Marion Leclerc, Marion LenoirAbstract: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 in- flammatory colitis scores and a gas chromatography-time offlight (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, myeloperoxi- dase (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 chemi- cal reactions. Some of them, belonging to the ammonia (-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the func- tional 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. IMPORTANCE Inflammatory bowel diseases (IBD) are characterized by low proportions of F. prausnitzii in the gut microbiome. This commensal bacterium exhibits anti-inflammatory effects through still unknown mechanisms. Stable monoassociated ro- dents are actually not a reproducible model to decipher F. prausnitzii protective effects. We propose a new gnotobiotic rodent model providing mechanistic clues. In this model, F. prausnitzii exhibits protective effects against an acute colitis and a protec- tive metabolic profile is linked to its presence along the digestive tract. We identified a molecule, salicylic acid, directly involved in the protective effect of F. prausnitzii. Targeting its metabolic pathways could be an attractive therapeutic strategy in IBD.
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Faecalibacterium prausnitzii prevents physiological damages in a chronic low grade inflammation murine model
BMC Microbiology, 2015Co-Authors: Sylvie Miquel, Florian Chain, Rebeca Martin, Jane M Natividad, Jennifer Jury, Harry SokolAbstract:The human gut houses one of the most complex and abundant ecosystems composed of up to 1013-1014 microorganisms. The importance of this intestinal microbiota is highlighted when a disruption of the intestinal ecosystem equilibrium appears (a phenomenon called dysbiosis) leading to an illness status, such as inflammatory bowel diseases (IBD). Indeed, the reduction of the commensal bacterium Faecalibacterium prausnitzii (one of the most prevalent intestinal bacterial species in healthy adults) has been correlated with several diseases, including IBD, and most importantly, it has been shown that this bacterium has anti-inflammatory and protective effects in pre-clinical models of colitis. Some dysbiosis disorders are characterized by functional and physiological alterations. Here, we report the beneficial effects of F. prausnitzii in the physiological changes induced by a chronic low-grade inflammation in a murine model. Chronic low-grade inflammation and gut dysfunction were induced in mice by two episodes of dinitro-benzene sulfonic acid (DNBS) instillations. Markers of inflammation, gut permeability, colonic serotonin and cytokine levels were studied. The effects of F. prausnitzii strain A2-165 and its culture supernatant (SN) were then investigated. No significant differences were observed in classical inflammation markers confirming that inflammation was subclinical. However, gut permeability, colonic serotonin levels and the colonic levels of the cytokines IL-6, INF-γ, IL-4 and IL-22 were higher in DNBS-treated than in untreated mice. Importantly, mice treated with either F. prausnitzii or its SN exhibited significant decreases in intestinal permeability, tissue cytokines and serotonin levels. Our results show that F. prausnitzii and its SN had beneficial effects on intestinal epithelial barrier impairment in a chronic low-grade inflammation model. These observations confirm the potential of this bacterium as a novel probiotic treatment in the management of gut dysfunction and low-grade inflammation.
