84 results on '"Chain, F."'
Search Results
2. Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery
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Barone, M., Ramayo-Caldas, Y., Estellé, J., Tambosco, K., Chadi, S., Maillard, F., Gallopin, M., Planchais, J., Chain, F., Kropp, C., Rios-Covian, D., Sokol, H., Brigidi, P., Langella, P., and Martín, R.
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- 2023
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3. Over-production of exopolysaccharide by Lacticaseibacillus rhamnosus CNCM I-3690 strain cutbacks its beneficial effect on the host
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Martín, R., Benítez-Cabello, A., Kulakauskas, S., Viana, M. V. C., Chamignon, C., Courtin, P., Carbonne, C., Chain, F., Pham, H. P., Derrien, Muriel, Bermúdez-Humarán, L. G., Chapot-Chartier, M. P., Smokvina, T., and Langella, P.
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- 2023
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4. Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime
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Leyrolle, Q., Decoeur, F., Briere, G., Amadieu, C., Quadros, A. R. A. A., Voytyuk, I., Lacabanne, C., Benmamar-Badel, A., Bourel, J., Aubert, A., Sere, A., Chain, F., Schwendimann, L., Matrot, B., Bourgeois, T., Grégoire, S., Leblanc, J. G., De Moreno De Leblanc, A., Langella, P., Fernandes, G. R., Bretillon, L., Joffre, C., Uricaru, R., Thebault, P., Gressens, P., Chatel, J. M., Layé, S., and Nadjar, A.
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- 2021
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5. Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime
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Leyrolle, Q., primary, Decoeur, F., additional, Briere, G., additional, Amadieu, C., additional, Quadros, A. R. A. A., additional, Voytyuk, I., additional, Lacabanne, C., additional, Benmamar-Badel, A., additional, Bourel, J., additional, Aubert, A., additional, Sere, A., additional, Chain, F., additional, Schwendimann, L., additional, Matrot, B., additional, Bourgeois, T., additional, Grégoire, S., additional, Leblanc, J. G., additional, De Moreno De Leblanc, A., additional, Langella, P., additional, Fernandes, G. R., additional, Bretillon, L., additional, Joffre, C., additional, Uricaru, R., additional, Thebault, P., additional, Gressens, P., additional, Chatel, J. M., additional, Layé, S., additional, and Nadjar, A., additional
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- 2020
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6. Effect of combining two genes for partial resistance to Barley yellow dwarf virus-PAV (BYDV-PAV) derived from Thinopyrum intermedium in wheat
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Jahier, J., Chain, F., Barloy, D., Tanguy, A. -M., Lemoine, J., Riault, G., Margalé, E., Trottet, M., and Jacquot, E.
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- 2009
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7. Does HIV-2 infection provide cross-protection against HIV-1 infection?
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Ariyoshi, K., van der Loeff, Schim M., Sabally, S., Chain, F., Corrah, T., and Whittle, H.
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- 1997
8. DOLOR CERVICAL
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Ximena Ortega F, Christian Linderman R, Marcelo Gálvez, and Andrés Chain F
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Medical technology ,R855-855.5 - Published
- 2007
9. Extensive copy-number variation of young genes across stickleback populations
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Chain, F. J. J., Feulner, P. G. D., Panchal, M., Eizaguirre, Christophe, Samonte, I. E., Kalbe, M., Lenz, T. L., Stoll, M., Bornberg-Bauer, E., Milinski, M., and Reusch, Thorsten B.H.
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lcsh:Genetics ,lcsh:QH426-470 - Abstract
Duplicate genes emerge as copy-number variations (CNVs) at the population level, and remain copy-number polymorphic until they are fixed or lost. The successful establishment of such structural polymorphisms in the genome plays an important role in evolution by promoting genetic diversity, complexity and innovation. To characterize the early evolutionary stages of duplicate genes and their potential adaptive benefits, we combine comparative genomics with population genomics analyses to evaluate the distribution and impact of CNVs across natural populations of an eco-genomic model, the three-spined stickleback. With whole genome sequences of 66 individuals from populations inhabiting three distinct habitats, we find that CNVs generally occur at low frequencies and are often only found in one of the 11 populations surveyed. A subset of CNVs, however, displays copy-number differentiation between populations, showing elevated within-population frequencies consistent with local adaptation. By comparing teleost genomes to identify lineage-specific genes and duplications in sticklebacks, we highlight rampant gene content differences among individuals in which over 30% of young duplicate genes are CNVs. These CNV genes are evolving rapidly at the molecular level and are enriched with functional categories associated with environmental interactions, depicting the dynamic early copy-number polymorphic stage of genes during population differentiation.
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- 2014
10. Genome-wide patterns of standing genetic variation in a marine population of three-spined sticklebacks
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Feulner, P., Chain, F., Panchal, M., Eizaguirre, C., Kalbe, M., Lenz, T., Mundry, M., Samonte, I., Stoll, M., Milinski, M., Reusch, T., and Bornberg-Bauer, E.
- Abstract
Since the end of the Pleistocene, the three-spined stickleback (Gasterosteus aculeatus) has repeatedly colonized and adapted to various freshwater habitats probably originating from ancestral marine populations. Standing genetic variation and the underlying genomic architecture both have been speculated to contribute to recent adaptive radiations of sticklebacks. Here, we expand on the current genomic resources of this fish by providing extensive genome-wide variation data from six individuals from a marine (North Sea) stickleback population. Using next-generation sequencing and a combination of pairedend and mate-pair libraries, we detected a wide size range of genetic variation. Among the six individuals, we found more than 7% of the genome is polymorphic, consisting of 2 599 111 SNPs, 233 464 indels and structural variation (SV) (>50 bp) such as 1054 copynumber variable regions (deletions and duplications) and 48 inversions. Many of these polymorphisms affect gene and coding sequences. Based on SNP diversity, we determined outlier regions concordant with signatures expected under adaptive evolution. As some of these outliers overlap with pronounced regions of copy-number variation, we propose the consideration of such SV when analysing SNP data from re-sequencing approaches. We further discuss the value of this resource on genome-wide variation for further investigation upon the relative contribution of standing variation on the parallel evolution of sticklebacks and the importance of the genomic architecture in adaptive radiation.
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- 2013
11. PCR cycles above routine numbers do not compromise high-throughput DNA barcoding results.
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Vierna, J., Doña, J., Vizcaíno, A., Serrano, D., Jovani, R., and Chain, F.
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GENETIC barcoding ,POLYMERASE chain reaction ,CEPHALOPODA ,CHIMERISM ,POINT mutation (Biology) ,PLANTS - Abstract
Copyright of Genome is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2017
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12. The odds of duplicate gene persistence after polyploidization
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Chain, F., Dushoff, J., and Evans, B.
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Evolution, Molecular ,Polyploidy ,lcsh:Genetics ,Species Specificity ,lcsh:QH426-470 ,Gene Duplication ,lcsh:Biotechnology ,lcsh:TP248.13-248.65 ,Genetics ,Animals ,Anura ,Biotechnology ,Research Article - Abstract
Background Gene duplication is an important biological phenomenon associated with genomic redundancy, degeneration, specialization, innovation, and speciation. After duplication, both copies continue functioning when natural selection favors duplicated protein function or expression, or when mutations make them functionally distinct before one copy is silenced. Results Here we quantify the degree to which genetic parameters related to gene expression, molecular evolution, and gene structure in a diploid frog - Silurana tropicalis - influence the odds of functional persistence of orthologous duplicate genes in a closely related tetraploid species - Xenopus laevis. Using public databases and 454 pyrosequencing, we obtained genetic and expression data from S. tropicalis orthologs of 3,387 X. laevis paralogs and 4,746 X. laevis singletons - the most comprehensive dataset for African clawed frogs yet analyzed. Using logistic regression, we demonstrate that the most important predictors of the odds of duplicate gene persistence in the tetraploid species are the total gene expression level and evenness of expression across tissues and development in the diploid species. Slow protein evolution and information density (fewer exons, shorter introns) in the diploid are also positively correlated with duplicate gene persistence in the tetraploid. Conclusions Our findings suggest that a combination of factors contribute to duplicate gene persistence following whole genome duplication, but that the total expression level and evenness of expression across tissues and through development before duplication are most important. We speculate that these parameters are useful predictors of duplicate gene longevity after whole genome duplication in other taxa.
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- 2011
13. Lactobacillus rhamnosusCNCM I-3690 and the commensal bacteriumFaecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice
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Laval, L, primary, Martin, R, additional, Natividad, JN, additional, Chain, F, additional, Miquel, S, additional, de Maredsous, C Desclée, additional, Capronnier, S, additional, Sokol, H, additional, Verdu, EF, additional, van Hylckama Vlieg, JET, additional, Bermúdez-Humarán, LG, additional, Smokvina, T, additional, and Langella, P, additional
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- 2015
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14. DOLOR CERVICAL
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Ortega F, Ximena, Linderman R, Christian, Gálvez, Marcelo, and Chain F, Andrés
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- 2007
15. DOLOR CERVICAL
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Ortega F,Ximena, Linderman R,Christian, Gálvez,Marcelo, and Chain F,Andrés
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- 2007
16. A Comprehensive Transcriptomic Analysis of the Effect of Silicon on Wheat Plants Under Control and Pathogen Stress Conditions
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Chain, F., primary, Côté-Beaulieu, C., additional, Belzile, F., additional, Menzies, J. G., additional, and Bélanger, R. R., additional
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- 2009
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17. Effect of combining two genes for partial resistance toBarley yellow dwarf virus-PAV (BYDV-PAV) derived fromThinopyrum intermediumin wheat
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Jahier, J., primary, Chain, F., additional, Barloy, D., additional, Tanguy, A. -M., additional, Lemoine, J., additional, Riault, G., additional, Margalé, E., additional, Trottet, M., additional, and Jacquot, E., additional
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- 2009
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18. Identification of Genes Potentially Involved in the Biocontrol Activity of Pseudozyma flocculosa
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Marchand, G., primary, Rémus-Borel, W., additional, Chain, F., additional, Hammami, W., additional, Belzile, F., additional, and Bélanger, R. R., additional
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- 2009
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19. Lactobacillus rhamnosus CNCM I-3690 and the commensal bacterium Faecalibacterium prausnitzii A2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice.
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Laval, L, Martin, R, Natividad, JN, Chain, F, Miquel, S, de Maredsous, C Desclée, Capronnier, S, Sokol, H, Verdu, EF, van Hylckama Vlieg, JET, Bermúdez-Humarán, LG, Smokvina, T, and Langella, P
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- 2015
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20. Lactobacillus rhamnosusCNCM I-3690 and the commensal bacterium Faecalibacterium prausnitziiA2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice
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Laval, L, Martin, R, Natividad, JN, Chain, F, Miquel, S, de Maredsous, C Desclée, Capronnier, S, Sokol, H, Verdu, EF, van Hylckama Vlieg, JET, Bermúdez-Humarán, LG, Smokvina, T, and Langella, P
- Abstract
Impaired gut barrier function has been reported in a wide range of diseases and syndromes and in some functional gastrointestinal disorders. In addition, there is increasing evidence that suggests the gut microbiota tightly regulates gut barrier function and recent studies demonstrate that probiotic bacteria can enhance barrier integrity. Here, we aimed to investigate the effects of Lactobacillus rhamnosusCNCM I-3690 on intestinal barrier function. In vitroresults using a Caco-2 monolayer cells stimulated with TNF-α confirmed the anti-inflammatory nature of the strain CNCM I-3690 and pointed out a putative role for the protection of the epithelial function. Next, we tested the protective effects of L. rhamnosusCNCM I-3690 in a mouse model of increased colonic permeability. Most importantly, we compared its performance to that of the well-known beneficial human commensal bacterium Faecalibacterium prauznitziiA2-165. Increased colonic permeability was normalized by both strains to a similar degree. Modulation of apical tight junction proteins expression was then analyzed to decipher the mechanism underlying this effect. We showed that CNCM I-3690 partially restored the function of the intestinal barrier and increased the levels of tight junction proteins Occludin and E-cadherin. The results indicate L. rhamnosusCNCM I-3690 is as effective as the commensal anti-inflammatory bacterium F. prausnitziito treat functional barrier abnormalities.
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- 2015
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21. DOLOR CERVICAL
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Ximena Ortega F, Christian Linderman R, Marcelo Gálvez, and Andrés Chain F
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Medical technology ,R855-855.5 - Full Text
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22. A NEW DEFINITION OF SOCIAL INSTITUTIONS.
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Chain, F. Stuart
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SOCIAL institutions ,CULTURE ,SOCIAL structure ,SOCIAL systems ,PHYSICAL anthropology ,PSYCHOLOGY ,BEHAVIOR - Abstract
Man is not only a tool-making animal, he is an institution-making animal. Of the three phases of culture which one has selected for analysis, social institutions remain. There have been many definitions of institutions and in a general way one knows what he means when he uses the word. Some students have found it important to distinguish between the function of an institution and its structure. A scholar has attempted an analysis of political institutions and comes to the conclusion that social structure from the psychological standpoint, is reducible to common and reciprocating attitudes of individuals and variations in such attitudes as to both content and degree of generality. Thus the structure of a social institution is reduced to a form of behavior. It is obvious, of course, that social institutions are significant as they influence or express human behavior, but the social institution is also a culture complex and this utility of characteristic human behavior and associated culture complex is sufficiently definite so that one recognize such different institutions as the family, the state, religion, industry and a host of lesser forms. In order to give body to the idea or concept of the social institution.
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- 1928
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23. Time-Restricted Feeding Potentiates the Ability of Lacticaseibacillus casei to Enrich the Retina in Omega-3 Fatty Acids.
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Lapaquette P, Boucard AS, Chain F, Grégoire S, Bermúdez-Humarán LG, Acar N, and Bringer MA
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- 2023
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24. Ligilactobacillus salivarius CNCM I-4866, a potential probiotic candidate, shows anti-inflammatory properties in vitro and in vivo .
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Carbonne C, Chadi S, Kropp C, Molimard L, Chain F, Langella P, and Martin R
- Abstract
Introduction: The aim of this work was to characterize a new strain of Ligilactobacillus salivarius (CNCM I-4866) (CNCM I-4866) to address its potential as probiotic with a special focus on intestinal inflammation. Potential anti-inflammatory abilities of this strain were evaluated through in vivo and in vitro experiments., Methods: Firstly, the strain was tested in a murine acute inflammation colitis model induced by DNBS. In vitro characterization was then performed with diverse tests: modulation capability of intestinal permeability; study of the impact on immunity profile through cytokines dosage; capacity to inhibit pathogens and adhere to intestinal cells lines. Production of metabolites, antibiotic resistance and survival to gastro-intestinal tract conditions were also tested., Results: In vitro assay has shown a reduction of colonic damage and markers of inflammation after treatment with CNCM I-4866. Transcriptomic analysis performed on colons showed the capacity of the strain to down-regulate pro-inflammatory cytokines. L. salivarius CNCM I-4866 exerted anti-inflammatory profile by reducing IL-8 production by TNF-α stimulated cell and modulated cytokines profile on peripheral blood mononuclear cells (PBMC). It protected intestinal integrity by increasing trans-epithelial electrical resistance (TEER) on Caco-2 TNF-α inflamed cells. Additionally, L. salivarius CNCM I-4866 displayed inhibition capacity on several intestinal pathogens and adhered to eukaryotic cells. Regarding safety and technical concerns, CNCM I-4866 was highly resistant to 0.3% of bile salts and produced mainly L-lactate. Finally, strain genomic characterization allowed us to confirm safety aspect of our strain, with no antibiotic gene resistance found., Discussion: Taken together, these results indicate that L. salivarius CNCM I-4866 could be a good probiotic candidate for intestinal inflammation, especially with its steady anti-inflammatory profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Carbonne, Chadi, Kropp, Molimard, Chain, Langella and Martin.)
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- 2023
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25. From In Vitro to In Vivo: A Rational Flowchart for the Selection and Characterization of Candidate Probiotic Strains in Intestinal Disorders.
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Maillard F, Meynier M, Mondot S, Pepke F, Galbert C, Torres Maravilla E, Kropp C, Sokol H, Carvalho FA, Jacouton E, Holowacz S, Langella P, Chain F, and Martín R
- Abstract
Experimental and clinical evidence has demonstrated the potential of probiotic strains in the prevention or treatment of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, there is little data on what the methodology leading to the identification of such strains should be. In this work, we propose a new flowchart to identify strains with probiotic potential for the management of IBS and IBD, which we tested on a collection of 39 lactic acid bacteria and Bifidobacteria strains. This flowchart included in vitro tests of immunomodulatory properties on intestinal and peripheral blood mononuclear cells (PBMCs), assessment of the barrier-strengthening effect by measuring transepithelial electric resistance (TEER) and quantification of short-chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists produced by the strains. The in vitro results were then combined in a principal component analysis (PCA) to identify strains associated with an anti-inflammatory profile. To validate our flowchart, we tested the two most promising strains identified in the PCA in mouse models of post-infectious IBS or chemically induced colitis to mimic IBD. Our results show that this screening strategy allows the identification of strains with potential beneficial effects on colonic inflammation and colonic hypersensitivity.
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- 2023
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26. An Isolate of Streptococcus mitis Displayed In Vitro Antimicrobial Activity and Deleterious Effect in a Preclinical Model of Lung Infection.
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Mathieu E, Marquant Q, Chain F, Bouguyon E, Saint-Criq V, Le-Goffic R, Descamps D, Langella P, Tompkins TA, Binda S, and Thomas M
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- Infant, Newborn, Humans, Staphylococcus aureus, Streptococcus mitis, Bacteria, Haemophilus influenzae, Anti-Bacterial Agents pharmacology, Lung, Respiratory Tract Infections drug therapy, Respiratory Tract Infections microbiology, Pneumonia, Staphylococcal Infections
- Abstract
Microbiota studies have dramatically increased over these last two decades, and the repertoire of microorganisms with potential health benefits has been considerably enlarged. The development of next generation probiotics from new bacterial candidates is a long-term strategy that may be more efficient and rapid with discriminative in vitro tests. Streptococcus strains have received attention regarding their antimicrobial potential against pathogens of the upper and, more recently, the lower respiratory tracts. Pathogenic bacterial strains, such as non-typable Haemophilus influenzae ( NTHi ), Pseudomonas aeruginosa ( P. aeruginosa ) and Staphylococcus aureus ( S. aureus ), are commonly associated with acute and chronic respiratory diseases, and it could be interesting to fight against pathogens with probiotics. In this study, we show that a Streptococcus mitis ( S. mitis ) EM-371 strain, isolated from the buccal cavity of a human newborn and previously selected for promising anti-inflammatory effects, displayed in vitro antimicrobial activity against NTHi , P. aeruginosa or S. aureus . However, the anti-pathogenic in vitro activity was not sufficient to predict an efficient protective effect in a preclinical model. Two weeks of treatment with S. mitis EM-371 did not protect against, and even exacerbated, NTHi lung infection.
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- 2023
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27. Lactococcus lactis engineered to deliver hCAP18 cDNA alleviates DNBS-induced colitis in C57BL/6 mice by promoting IL17A and IL10 cytokine expression.
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Noguès EB, Kropp C, Bétemps L, de Sousa C, Chain F, Auger S, Azevedo V, Langella P, and Chatel JM
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- Animals, Cytokines metabolism, DNA, Complementary metabolism, Dinitrofluorobenzene analogs & derivatives, Interleukin-10 genetics, Interleukin-10 metabolism, Interleukin-17 metabolism, Mice, Mice, Inbred C57BL, Cathelicidins metabolism, Colitis chemically induced, Colitis genetics, Colitis therapy, Lactococcus lactis genetics, Lactococcus lactis metabolism
- Abstract
With its antimicrobial and immunomodulating properties, the cathelicidin (LL37) plays an important role in innate immune system. Here, we attempted to alleviate chemically induced colitis using a lactococci strain that either directly expressed the precursor to LL37, hCAP18 (LL-pSEC:hCAP18), or delivered hCAP18 cDNA to host cells under the control of the cytomegalovirus promoter (LL-Probi-H1:hCAP18). We also investigated whether the alleviation of symptoms could be explained through modification of the gut microbiota by hCAP18. Mice were administered daily doses of LL-pSEC:hCAP18 or LL-Probi-H1:hCAP18. On day 7, colitis was induced by DNBS. During autopsy, we assessed macroscopic tissue damage in the colon and collected tissue samples for the characterization of inflammation markers and histological analysis. Feces were collected at day 7 for 16S DNA sequencing. We also performed a fecal transplant experiment in which mice underwent colon washing and received feces from Lactococcus lactis-treated mice before DNBS-colitis induction. Treatment with LL-Probi-H1:hCAP18 reduced the severity of colitis symptoms. The protective effects were accompanied by increased levels of IL17A and IL10 in mesenteric lymph node cells. L. lactis administration altered the abundance of Lachnospiraceae and Muribaculaceae. However, fecal transplant from L. lactis-treated mice did not improve DNBS-induced symptoms in recipient mice., (© 2022. The Author(s).)
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- 2022
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28. The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo.
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Kropp C, Le Corf K, Relizani K, Tambosco K, Martinez C, Chain F, Rawadi G, Langella P, Claus SP, and Martin R
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- Animals, Caco-2 Cells, Disease Models, Animal, HT29 Cells, Humans, Male, Mice, Anti-Inflammatory Agents pharmacology, Clostridiales, Colitis chemically induced, Colitis metabolism, Colitis therapy, Intestinal Mucosa metabolism, Intestinal Mucosa microbiology
- Abstract
Christensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.
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- 2021
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29. Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3 .
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Lenoir M, Martín R, Torres-Maravilla E, Chadi S, González-Dávila P, Sokol H, Langella P, Chain F, and Bermúdez-Humarán LG
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- Adaptor Proteins, Signal Transducing genetics, Animals, Colon metabolism, Colon microbiology, Gene Expression Profiling, HT29 Cells, Humans, Interleukin-8 metabolism, Intestinal Mucosa cytology, Intestinal Mucosa metabolism, Male, Mice, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha metabolism, Up-Regulation, Adaptor Proteins, Signal Transducing metabolism, Butyrates metabolism, Faecalibacterium prausnitzii physiology, Gastrointestinal Microbiome, Inflammation metabolism, Inflammation microbiology, Intestinal Mucosa microbiology
- Abstract
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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- 2020
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30. Adamantane Containing Peptidoglycan Fragments Enhance RANTES and IL-6 Production in Lipopolysaccharide-Induced Macrophages.
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Manček-Keber M, Ribić R, Chain F, Sinnaeve D, Martins JC, Jerala R, Tomić S, and Fehér K
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- Animals, Cells, Cultured, Macrophages drug effects, Macrophages immunology, Mice, Mice, Inbred C57BL, Peptidoglycan chemistry, Adamantane chemistry, Chemokine CCL5 metabolism, Interleukin-6 metabolism, Lipopolysaccharides pharmacology, Macrophages metabolism, Peptidoglycan pharmacology
- Abstract
We report the enhancement of the lipopolysaccharide-induced immune response by adamantane containing peptidoglycan fragments in vitro. The immune stimulation was detected by Il-6 (interleukine 6) and RANTES (regulated on activation, normal T cell expressed and secreted) chemokine expression using cell assays on immortalized mouse bone-marrow derived macrophages. The most active compound was a α-D-mannosyl derivative of an adamantylated tripeptide with L-chirality at the adamantyl group attachment, whereby the mannose moiety assumed to target mannose receptors expressed on macrophage cell surfaces. The immune co-stimulatory effect was also influenced by the configuration of the adamantyl center, revealing the importance of specific molecular recognition event taking place with its receptor. The immunostimulating activities of these compounds were further enhanced upon their incorporation into lipid bilayers, which is likely related to the presence of the adamantyl group that helps anchor the peptidoglycan fragment into lipid nanoparticles. We concluded that the proposed adamantane containing peptidoglycan fragments act as co-stimulatory agents and are also suitable for the preparation of lipid nanoparticle-based delivery of peptidoglycan fragments.
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- 2020
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31. Capsular Polysaccharide Cross-Regulation Modulates Bacteroides thetaiotaomicron Biofilm Formation.
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Béchon N, Mihajlovic J, Vendrell-Fernández S, Chain F, Langella P, Beloin C, and Ghigo JM
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- Animals, Bacterial Adhesion genetics, Bacterial Capsules chemistry, Gene Expression Regulation, Bacterial, Male, Mice, Mice, Inbred C3H, Mutagenesis, Specific Pathogen-Free Organisms, Bacterial Capsules genetics, Bacteroides thetaiotaomicron genetics, Bacteroides thetaiotaomicron physiology, Biofilms growth & development, Polysaccharides, Bacterial chemistry
- Abstract
Bacteroides thetaiotaomicron is one of the most abundant gut symbiont species, whose contribution to host health through its ability to degrade dietary polysaccharides and mature the immune system is under intense scrutiny. In contrast, adhesion and biofilm formation, which are potentially involved in gut colonization and microbiota structure and stability, have hardly been investigated in this intestinal bacterium. To uncover B. thetaiotaomicron biofilm-related functions, we performed a transposon mutagenesis in the poorly biofilm-forming reference strain VPI-5482 and showed that capsule 4, one of the eight B. thetaiotaomicron capsules, hinders biofilm formation. We then showed that the production of capsules 1, 2, 3, 5, and 6 also inhibits biofilm formation and that decreased capsulation of the population correlated with increased biofilm formation, suggesting that capsules could be masking adhesive surface structures. In contrast, we showed that capsule 8 displayed intrinsic adhesive properties. Finally, we demonstrated that BT2934 , the wzx homolog of the B. thetaiotaomicron glycosylation locus, competes with capsule production and impacts its adhesion capacity. This study therefore establishes B. thetaiotaomicron capsule regulation as a major determinant of B. thetaiotaomicron biofilm formation, providing new insights into how modulation of different B. thetaiotaomicron surface structures affects in vitro biofilm formation. IMPORTANCE The human gut harbors a complex bacterial community that plays important roles in host health and disease, including nutrient acquisition, maturation of the immune system, and resistance to infections. The capacity to adhere to surfaces and form communities called biofilms is believed to be important for niche colonization and maintenance of gut bacteria. However, little is known about the adhesion capacity of most gut bacteria. In this study, we investigated biofilm formation in Bacteroides thetaiotaomicron , one of the most abundant bacteria of the normal mammalian intestine. We identified that B. thetaiotaomicron capsules, a group of eight surface-exposed polysaccharidic layers mediating important interactions with the gut environment, are also major determinants of biofilm formation that mask or unmask adhesion factors. Studying how B. thetaiotaomicron regulates its adhesion properties will allow us to better understand the physiology and specific properties of this important gut symbiont within anaerobic biofilms., (Copyright © 2020 Béchon et al.)
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- 2020
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32. Targeted Delivery of Adamantylated Peptidoglycan Immunomodulators in Lipid Nanocarriers: NMR Shows That Cargo Fragments Are Available on the Surface.
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Ribić R, Manček-Keber M, Chain F, Sinnaeve D, Martins JC, Jerala R, Tomić S, and Fehér K
- Subjects
- Immunologic Factors, Magnetic Resonance Spectroscopy, Mannose, Cell Wall, Peptidoglycan
- Abstract
We present an in-depth investigation of the membrane interactions of peptidoglycan (PGN)-based immune adjuvants designed for lipid-based delivery systems using NMR spectroscopy. The derivatives contain a cargo peptidoglycan (PGN) dipeptide fragment and an adamantyl group, which serves as an anchor to the lipid bilayer. Furthermore, derivatives with a mannose group that can actively target cell surface receptors on immune cells are also studied. We showed that the targeting mannose group and the cargo PGN fragment are both available on the lipid bilayer surface, thereby enabling interactions with cognate receptors. We found that the nonmannosylated compounds are incorporated stronger into the lipid assemblies than the mannosylated ones, but the latter compounds penetrate deeper in the bilayer. This might be explained by stronger electrostatic interactions available for zwitterionic nonmannosylated derivatives as opposed to the compounds in which the charged N-terminus is capped by mannose groups. The higher incorporation efficiency of the nonmannosylated compounds correlated with a larger relative enhancement in immune stimulation activities upon lipid incorporation compared to that of the derivatives with the mannose group. The chirality of the adamantyl group also influenced the incorporation efficiency, which in turn correlated with membrane-associated conformations that affect possible intermolecular interactions with lipid molecules. These findings will help in improving the development of PGN-based immune adjuvants suitable for delivery in lipid nanoparticles.
- Published
- 2020
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33. Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition.
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Albouery M, Buteau B, Grégoire S, Cherbuy C, Pais de Barros JP, Martine L, Chain F, Cabaret S, Berdeaux O, Bron AM, Acar N, Langella P, and Bringer MA
- Subjects
- Age Factors, Animals, Cholesterol metabolism, Fatty Acid Desaturases genetics, Fatty Acid Elongases genetics, Fatty Acids metabolism, Fatty Acids, Monounsaturated metabolism, Fatty Acids, Unsaturated metabolism, Gastrointestinal Microbiome genetics, Gene Expression, Germ-Free Life, Lipids, Liver metabolism, Male, Mice, Stearoyl-CoA Desaturase genetics, Aging metabolism, Brain metabolism, Gastrointestinal Microbiome physiology, Lipid Metabolism
- Abstract
Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis ( Scd1, Fads1, Fads2, Elovl2 , and Elovl5 ) was dysregulated in mice inoculated with an aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status., (Copyright © 2020 Albouery, Buteau, Grégoire, Cherbuy, Pais de Barros, Martine, Chain, Cabaret, Berdeaux, Bron, Acar, Langella and Bringer.)
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- 2020
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34. A Putative Type V Pilus Contributes to Bacteroides thetaiotaomicron Biofilm Formation Capacity.
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Mihajlovic J, Bechon N, Ivanova C, Chain F, Almeida A, Langella P, Beloin C, and Ghigo JM
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- Animals, Bacterial Adhesion physiology, Gastrointestinal Microbiome physiology, Humans, Male, Mice, Mice, Inbred C3H, Bacteroides thetaiotaomicron physiology, Biofilms growth & development, Fimbriae, Bacterial physiology
- Abstract
Bacteroides thetaiotaomicron is a prominent anaerobic member of the healthy human gut microbiota. While the majority of functional studies on B. thetaiotaomicron addressed its impact on the immune system and the utilization of diet polysaccharides, B. thetaiotaomicron biofilm capacity and its contribution to intestinal colonization are still poorly characterized. We tested the natural adhesion of 34 B. thetaiotaomicron isolates and showed that although biofilm capacity is widespread among B. thetaiotaomicron strains, this phenotype is masked or repressed in the widely used reference strain VPI 5482. Using transposon mutagenesis followed by a biofilm positive-selection procedure, we identified VPI 5482 mutants with increased biofilm capacity corresponding to an alteration in the C-terminal region of BT3147, encoded by the BT3148-BT3147 locus, which displays homology with Mfa-like type V pili found in many Bacteroidetes We show that BT3147 is exposed on the B. thetaiotaomicron surface and that BT3147-dependent adhesion also requires BT3148, suggesting that BT3148 and BT3147 correspond to the anchor and stalk subunits of a new type V pilus involved in B. thetaiotaomicron adhesion. This study therefore introduces B. thetaiotaomicron as a model to study proteinaceous adhesins and biofilm-related phenotypes in this important intestinal symbiont. IMPORTANCE Although the gut anaerobe Bacteroides thetaiotaomicron is a prominent member of the healthy human gut microbiota, little is known about its capacity to adhere to surfaces and form biofilms. Here, we identify that alteration of a surface-exposed protein corresponding to a type of pili found in many Bacteroidetes increases B. thetaiotaomicron biofilm formation. This study lays the ground for establishing this bacterium as a model organism for in vitro and in vivo studies of biofilm-related phenotypes in gut anaerobes., (Copyright © 2019 American Society for Microbiology.)
- Published
- 2019
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35. The commensal Escherichia coli CEC15 reinforces intestinal defences in gnotobiotic mice and is protective in a chronic colitis mouse model.
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Escribano-Vazquez U, Verstraeten S, Martin R, Chain F, Langella P, Thomas M, and Cherbuy C
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- Animals, Benzenesulfonates administration & dosage, Benzenesulfonates toxicity, Chronic Disease, Colitis chemically induced, Colitis genetics, Colitis microbiology, Colon drug effects, Colon immunology, Colon microbiology, Colon pathology, Disease Models, Animal, Gene Expression Regulation immunology, Germ-Free Life, Humans, Interleukin-10 genetics, Interleukin-10 immunology, Intestinal Mucosa drug effects, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Male, Mice, Severity of Illness Index, Colitis immunology, Escherichia coli immunology, Gastrointestinal Microbiome immunology, Host Microbial Interactions immunology, Symbiosis immunology
- Abstract
Escherichia coli is a regular inhabitant of the gut microbiota throughout life. However, its role in gut health is controversial. Here, we investigated the relationship between the commensal E. coli strain CEC15 (CEC), which we previously isolated, and the intestine in homeostatic and disease-prone settings. The impact of CEC was compared to that of the probiotic E. coli Nissle 1917 (Nissle) strain. The expression of ileal and colonic genes that play a key role in intestinal homeostasis was higher in CEC- and Nissle-mono-associated wild-type mice than in germfree mice. This included genes involved in the turnover of reactive oxygen species, antimicrobial peptide synthesis, and immune responses. The impact of CEC and Nissle on such gene expression was stronger in a disease-prone setting, i.e. in gnotobiotic IL10-deficient mice. In a chronic colitis model, CEC more strongly decreased signs of colitis severity (myeloperoxidase activity and CD3
+ immune-cell infiltration) than Nissle. Thus, our study shows that CEC and Nissle contribute to increased expression of genes involved in the maintenance of gut homeostasis in homeostatic and inflammatory settings. We show that these E. coli strains, in particular CEC, can have a beneficial effect in a chronic colitis mouse model.- Published
- 2019
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36. The potential probiotic Lactobacillus rhamnosus CNCM I-3690 strain protects the intestinal barrier by stimulating both mucus production and cytoprotective response.
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Martín R, Chamignon C, Mhedbi-Hajri N, Chain F, Derrien M, Escribano-Vázquez U, Garault P, Cotillard A, Pham HP, Chervaux C, Bermúdez-Humarán LG, Smokvina T, and Langella P
- Subjects
- Animals, Caco-2 Cells, Colon drug effects, Colon metabolism, Colon pathology, Cytoprotection drug effects, Dinitrofluorobenzene analogs & derivatives, Gene Expression Profiling methods, Goblet Cells drug effects, Goblet Cells metabolism, HEK293 Cells, HT29 Cells, Humans, Inflammation chemically induced, Inflammation genetics, Inflammation metabolism, Intestines microbiology, Intestines physiology, Lacticaseibacillus rhamnosus genetics, Mice, Mutation, Permeability drug effects, Protective Agents pharmacology, Intestinal Mucosa metabolism, Intestines drug effects, Lacticaseibacillus rhamnosus physiology, Mucus metabolism, Probiotics pharmacology
- Abstract
The gut barrier plays an important role in human health. When barrier function is impaired, altered permeability and barrier dysfunction can occur, leading to inflammatory bowel diseases, irritable bowel syndrome or obesity. Several bacteria, including pathogens and commensals, have been found to directly or indirectly modulate intestinal barrier function. The use of probiotic strains could be an important landmark in the management of gut dysfunction with a clear impact on the general population. Previously, we found that Lactobacillus rhamnosus CNCM I-3690 can protect intestinal barrier functions in mice inflammation model. Here, we investigated its mechanism of action. Our results show that CNCM I-3690 can (i) physically maintain modulated goblet cells and the mucus layer and (ii) counteract changes in local and systemic lymphocytes. Furthermore, mice colonic transcriptome analysis revealed that CNCM I-3690 enhances the expression of genes related to healthy gut permeability: motility and absorption, cell proliferation; and protective functions by inhibiting endogenous proteases. Finally, SpaFED pili are clearly important effectors since an L. rhamnosus ΔspaF mutant failed to provide the same benefits as the wild type strain. Taken together, our data suggest that CNCM I-3690 restores impaired intestinal barrier functions via anti-inflammatory and cytoprotective responses.
- Published
- 2019
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37. Trends in DNA barcoding and metabarcoding.
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Adamowicz SJ, Boatwright JS, Chain F, Fisher BL, Hogg ID, Leese F, Lijtmaer DA, Mwale M, Naaum AM, Pochon X, Steinke D, Wilson JJ, Wood S, Xu J, Xu S, Zhou X, and van der Bank M
- Subjects
- Africa, Conservation of Natural Resources, Databases, Nucleic Acid, Phylogeny, Biodiversity, Biota, DNA Barcoding, Taxonomic trends, Evolution, Molecular
- Published
- 2019
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38. Anti-tumoral Effects of Recombinant Lactococcus lactis Strain Secreting IL-17A Cytokine.
- Author
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Jacouton E, Torres Maravilla E, Boucard AS, Pouderous N, Pessoa Vilela AP, Naas I, Chain F, Azevedo V, Langella P, and Bermúdez-Humarán LG
- Abstract
Interleukin-17A (IL-17A) is a pro-inflammatory cytokine produced by T
H17 cells that participates and contributes in host defense and autoimmune disease. We have recently reported antitumor properties of the probiotic strain of Lactobacillus casei BL23 in mice and TH17 cells was shown to play an important role in this beneficial effect. In order to better understand the role of IL-17A in cancer, we constructed a recombinant strain of Lactococcus lactis producing this cytokine and we determined its biological activity in: (i) a bioassay test for the induction of IL-6 production by murine fibroblasts 3T3 L1 cells line and (ii) in a mouse allograft model of human papilloma virus (HPV)-induced cancer. Our data show that recombinant L. lactis produces and efficiently secretes biologically active IL-17A cytokine. Interestingly, ∼26% of mice intranasally treated with L. lactis -IL-17A and challenged with TC-1 cells remained tumor free over the experiment, in contrast to control mice treated with the wild type strain of L. lactis which developed 100% of aggressive tumors. In addition, the median size of the ∼74% tumor-bearing mice treated with recombinant L. lactis -IL-17A, was significantly lower than mice treated with L. lactis -wt. Altogether, our results demonstrate that intranasal administration with L. lactis secreting IL-17A results in a partial protection against TC-1-induced tumors in mice, confirming antitumor effects of this cytokine in our cancer model.- Published
- 2019
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39. Elucidating the Immune-Related Mechanisms by Which Probiotic Strain Lactobacillus casei BL23 Displays Anti-tumoral Properties.
- Author
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Jacouton E, Michel ML, Torres-Maravilla E, Chain F, Langella P, and Bermúdez-Humarán LG
- Abstract
We have recently described antitumor properties of Lactobacillus casei BL23 strain in both a mouse allograft model of human papilloma virus (HPV)-induced cancer and dimethylhydrazine-associated colorectal cancer. However, the mechanisms underlying these beneficial effects are still unknown. Interestingly, in vitro cellular models show that this bacterium is able to stimulate the production of high levels of IL-2. Because this cytokine has well-known antitumor properties, we decided to explore its role in the anti-cancer effects of BL23 using the HPV-induced cancer model. We found a negative correlation between IL-2 and tumor size confirming the necessity of IL-2 to protect from tumor development. Then, we blocked IL-2 synthesis using neutralizing monoclonal antibodies in mice that were challenged with lethal levels of tumor cells; this led to a significant reduction in the protective abilities of BL23. Next, we used a genetically modified strain of Lactococcus lactis to deliver exogenous IL-2 to the system, and in doing so, we were able to partially mimic the antitumor properties of BL23. Additionally, we showed the systemic role of T-cells in tumor protection through a negative correlation between tumor size and T-cells subpopulations and an increasement of BL23-specific local Foxp3 levels in tumor-bearing mice. Finally, we observed a negative correlation between tumor size and NK+ cells, but local recruitment of NK cells and cytotoxic activity appeared specific to BL23 treatment. Taken together, our data suggest that IL-2 signaling pathway plays an important role in the anti-tumoral effects of probiotic strain L. casei BL23. These results encourage further investigation in the use of probiotic strains for potential therapeutic applications to clinical practice, in particular for the treatment of colorectal cancer. Furthermore, our approach could be extended and applied to other potential beneficial microorganisms, such as gut microbiota, in order to better understand the crosstalk between microbes and the host.
- Published
- 2019
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40. A New Bifidobacteria Expression SysTem (BEST) to Produce and Deliver Interleukin-10 in Bifidobacterium bifidum .
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Mauras A, Chain F, Faucheux A, Ruffié P, Gontier S, Ryffel B, Butel MJ, Langella P, Bermúdez-Humarán LG, and Waligora-Dupriet AJ
- Abstract
In the last years there has been a growing interest in the use of genetically modified bacteria to deliver molecules of therapeutic interest at mucosal surfaces. Due to the well-recognized probiotic properties of some strains, bifidobacteria represent excellent candidates for the development of live vehicles to produce and deliver heterologous proteins at mucosal surfaces. However, very few studies have considered this genus because of its complexity to be genetically manipulated. In this work, we report the development of a new Bifidobacteria Expression SysTem (BEST) allowing the production of heterologous proteins in Bifidobacterium bifidum . This system is based on: i) the broad host range plasmid pWV01, ii) a stress-inducible promoter, and iii) two different signal peptides (SPs) one issued from Lactococcus lactis (SP
Exp4 ) and issued from Bifidobacterium longum (SPBL1181 ). The functionality of BEST system was validated by cloning murine interleukin-10 (IL-10) and establishing the resulting plasmids (i.e., pBESTExp4 :IL-10 and pBESTBL1181 :IL-10) in the strain of B. bifidum BS42. We then demonstrated in vitro that recombinant B. bifidum BS42 harboring pBESTBL1181 :IL-10 plasmid efficiently secreted IL-10 and that this secretion was significantly higher (sevenfold) than its counterpart B. bifidum BS42 harboring pBESTExp4 :IL-10 plasmid. Finally, we validated in vivo that recombinant B. bifidum strains producing IL-10 using BEST system efficiently delivered this cytokine at mucosal surfaces and exhibit beneficial effects in a murine model of low-grade intestinal inflammation.- Published
- 2018
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41. Characterization of a Prophage-Free Derivative Strain of Lactococcus lactis ssp. lactis IL1403 Reveals the Importance of Prophages for Phenotypic Plasticity of the Host.
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Aucouturier A, Chain F, Langella P, and Bidnenko E
- Abstract
Lactococcus lactis is a lactic acid bacterium of major importance for the dairy industry and for human health. Recent sequencing surveys of this species have provided evidence that all lactococcal genomes contain prophages and prophage-like elements. The prophage-related sequences encompass up to 10% of the bacterial chromosomes and thus contribute significantly to the genetic diversity of lactococci. However, the impact of these resident prophages on the physiology of L. lactis is presently unknown. The genome of the first sequenced prototype strain, L. lactis ssp. lactis IL1403, contains six prophage-like elements which together represent 6.7% of the IL1403 chromosome. Diverse prophage genes other than those encoding phage repressors have been shown to be expressed in lysogenic conditions, suggesting that prophage genes are indeed able to modulate the physiology of their host. To elucidate the effect of resident prophages on the behavior of L. lactis in different growth conditions, we constructed and characterized, for the first time, a derivative strain of IL1403 that is prophage-free. This strain provides unique experimental opportunities for the study of different aspects of lactococcal physiology using the well-defined genetic background of IL1403. Here, we show that resident prophages modify the growth and survival of the host strain to a considerable extent in different conditions, including in the gastrointestinal environment. They also may affect cellular autolytic properties and the host cells' susceptibility to virulent bacteriophages and antimicrobial agents. It thus appears that prophages contribute significantly to lactococcal cell physiology and might play an important role in the adaptation of L. lactis to cultivation and environmental conditions.
- Published
- 2018
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42. A Versatile New Model of Chemically Induced Chronic Colitis Using an Outbred Murine Strain.
- Author
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Barone M, Chain F, Sokol H, Brigidi P, Bermúdez-Humarán LG, Langella P, and Martín R
- Abstract
Murine colitis models are crucial tools for understanding intestinal homeostasis and inflammation. However, most current models utilize a highly inbred strain of mice, and often only one sex is employed to limit bias. This targeted approach, which in itself is biased, means that murine genetic diversity and sex-related differences are ignored, making it even more difficult to extend findings to humans, who are highly heterogeneous. Furthermore, most models do not examine the chronic form of colitis, an important fact taking into account the chronic nature of the inflammatory bowel diseases (IBD). Here, we attempted to create a more realistic murine colitis model by addressing these three issues. Using chemically induced chronic colon inflammation in an outbred strain of mice (RjOrl:SWISS [CD-1]), we (i) mimicked the relapsing nature of the disease, (ii) better represented normal genetic variability, and (iii) employed both female and male mice. Colitis was induced by intrarectal administration of dinitrobenzene sulfonic acid (DNBS). After a recovery period and 3 days before the mice were euthanized, colitis was reactivated by a second administration of DNBS. Protocol length was 24 days. Colitis severity was assessed using body mass, macroscopic scores, and histological scores. Myeloperoxidase (MPO) activity, cytokine levels, and lymphocyte populations were also characterized. Our results show that the intrarectal administration of DNBS effectively causes colitis in both female and male CD-1 mice in a dose-dependent manner, as reflected by loss of body mass, macroscopic scores and histological scores. Furthermore, colon cytokine levels and mesenteric lymph node characteristics indicate that this model involves immune system activation. Although some variables were sex-specific, most of the results support including both females and males in the model. Our ultimate goal is to make this model available to researchers for testing candidate anti-inflammatory agents, such as classical or next-generation probiotics; we also aim for the results to be more easily transferrable to human trials.
- Published
- 2018
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43. Probiotic Strain Lactobacillus casei BL23 Prevents Colitis-Associated Colorectal Cancer.
- Author
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Jacouton E, Chain F, Sokol H, Langella P, and Bermúdez-Humarán LG
- Abstract
The gut microbiota plays a major role in intestinal health, and an imbalance in its composition can lead to chronic gut inflammation and a predisposition to developing colorectal cancer (CRC). Currently, the use of probiotic bacteria represents an emerging alternative to treat and prevent cancer. Moreover, consumption of these beneficial bacteria may also favorably modulate the composition of the gut microbiota, which has been described in several studies to play an important role in CRC carcinogenesis. In this context, the aim of this study was to assess the protective effect of oral treatment with Lactobacillus casei BL23, a probiotic strain well known for its anti-inflammatory and anticancer properties. First, CRC was induced in C57BL6 mice by a single intraperitoneal injection with azoxymethane (8 mg/kg), followed by four courses of dextran sodium sulfate (2.5%) in drinking water that were separated by an adjustable recovery period. At the time of sacrifice (day 46), tumor incidence, histological scores, and epithelial proliferation were determined in colon samples. Our results show that L. casei BL23 significantly protected mice against CRC development; specifically, L. casei BL23 treatment reduced histological scores and proliferative index values. In addition, our analysis revealed that L. casei BL23 had an immunomodulatory effect, mediated through the downregulation of the IL-22 cytokine, and an antiproliferative effect, mediated through the upregulation of caspase-7, caspase-9 , and Bik . Finally, L. casei BL23 treatment tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an analysis of fecal microbiota. Altogether our results demonstrate the high potential of L. casei BL23 for the development of new, probiotic-based strategies to fight CRC.
- Published
- 2017
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44. New Insights into the Diversity of the Genus Faecalibacterium .
- Author
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Benevides L, Burman S, Martin R, Robert V, Thomas M, Miquel S, Chain F, Sokol H, Bermudez-Humaran LG, Morrison M, Langella P, Azevedo VA, Chatel JM, and Soares S
- Abstract
Faecalibacterium prausnitzii is a commensal bacterium, ubiquitous in the gastrointestinal tracts of animals and humans. This species is a functionally important member of the microbiota and studies suggest it has an impact on the physiology and health of the host. F. prausnitzii is the only identified species in the genus Faecalibacterium , but a recent study clustered strains of this species in two different phylogroups. Here, we propose the existence of distinct species in this genus through the use of comparative genomics. Briefly, we performed analyses of 16S rRNA gene phylogeny, phylogenomics, whole genome Multi-Locus Sequence Typing (wgMLST), Average Nucleotide Identity (ANI), gene synteny, and pangenome to better elucidate the phylogenetic relationships among strains of Faecalibacterium . For this, we used 12 newly sequenced, assembled, and curated genomes of F. prausnitzii , which were isolated from feces of healthy volunteers from France and Australia, and combined these with published data from 5 strains downloaded from public databases. The phylogenetic analysis of the 16S rRNA sequences, together with the wgMLST profiles and a phylogenomic tree based on comparisons of genome similarity, all supported the clustering of Faecalibacterium strains in different genospecies. Additionally, the global analysis of gene synteny among all strains showed a highly fragmented profile, whereas the intra-cluster analyses revealed larger and more conserved collinear blocks. Finally, ANI analysis substantiated the presence of three distinct clusters-A, B, and C-composed of five, four, and four strains, respectively. The pangenome analysis of each cluster corroborated the classification of these clusters into three distinct species, each containing less variability than that found within the global pangenome of all strains. Here, we propose that comparison of pangenome subsets and their associated α values may be used as an alternative approach, together with ANI, in the in silico classification of new species. Altogether, our results provide evidence not only for the reconsideration of the phylogenetic and genomic relatedness among strains currently assigned to F. prausnitzii , but also the need for lineage (strain-based) differentiation of this taxon to better define how specific members might be associated with positive or negative host interactions.
- Published
- 2017
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45. Using murine colitis models to analyze probiotics-host interactions.
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Martín R, Chain F, Miquel S, Motta JP, Vergnolle N, Sokol H, and Langella P
- Subjects
- Animals, Bifidobacterium growth & development, Bifidobacterium metabolism, Colitis chemically induced, Dysbiosis microbiology, Gastrointestinal Microbiome physiology, Gastrointestinal Tract microbiology, Gastrointestinal Tract pathology, Humans, Lactobacillus growth & development, Lactobacillus metabolism, Mice, Colitis therapy, Disease Models, Animal, Probiotics therapeutic use
- Abstract
Probiotics are defined as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. So, to consider a microorganism as a probiotic, a demonstrable beneficial effect on the health host should be shown as well as an adequate defined safety status and the capacity to survive transit through the gastrointestinal tract and to storage conditions. In this review, we present an overview of the murine colitis models currently employed to test the beneficial effect of the probiotic strains as well as an overview of the probiotics already tested. Our aim is to highlight both the importance of the adequate selection of the animal model to test the potential probiotic strains and of the value of the knowledge generated by these in vivo tests., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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46. 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.
- Author
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Martín R, Miquel S, Benevides L, Bridonneau C, Robert V, Hudault S, Chain F, Berteau O, Azevedo V, Chatel JM, Sokol H, Bermúdez-Humarán LG, Thomas M, and Langella P
- Abstract
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 three 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.
- Published
- 2017
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47. Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria.
- Author
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LeBlanc JG, Chain F, Martín R, Bermúdez-Humarán LG, Courau S, and Langella P
- Subjects
- Adenosine Triphosphate biosynthesis, Adenosine Triphosphate metabolism, Animals, Butyrates metabolism, Dietary Fiber metabolism, Fatty Acids, Volatile biosynthesis, Fermentation, Food, Gastrointestinal Microbiome physiology, Gastrointestinal Tract microbiology, Humans, Mice, Vitamins biosynthesis, Energy Metabolism, Fatty Acids, Volatile metabolism, Probiotics metabolism, Symbiosis, Vitamins metabolism
- Abstract
The aim of this review is to summarize the effect in host energy metabolism of the production of B group vitamins and short chain fatty acids (SCFA) by commensal, food-grade and probiotic bacteria, which are also actors of the mammalian nutrition. The mechanisms of how these microbial end products, produced by these bacterial strains, act on energy metabolism will be discussed. We will show that these vitamins and SCFA producing bacteria could be used as tools to recover energy intakes by either optimizing ATP production from foods or by the fermentation of certain fibers in the gastrointestinal tract (GIT). Original data are also presented in this work where SCFA (acetate, butyrate and propionate) and B group vitamins (riboflavin, folate and thiamine) production was determined for selected probiotic bacteria.
- Published
- 2017
- Full Text
- View/download PDF
48. 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.
- Author
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Breyner NM, Michon C, de Sousa CS, Vilas Boas PB, Chain F, Azevedo VA, Langella P, and Chatel JM
- Abstract
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.
- Published
- 2017
- Full Text
- View/download PDF
49. Erratum to: Protective effect of TSLP delivered at the gut mucosa level by recombinant lactic acid bacteria in DSS-induced colitis mouse model.
- Author
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Aubry C, Michon C, Chain F, Chvatchko Y, Goffin L, Zimmerli SC, Leguin S, Langella P, Bermudez-Humaran L, and Chatel JM
- Published
- 2016
- Full Text
- View/download PDF
50. Bifidobacterium animalis ssp. lactis CNCM-I2494 Restores Gut Barrier Permeability in Chronically Low-Grade Inflamed Mice.
- Author
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Martín R, Laval L, Chain F, Miquel S, Natividad J, Cherbuy C, Sokol H, Verdu EF, van Hylckama Vlieg J, Bermudez-Humaran LG, Smokvina T, and Langella P
- Abstract
Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis ssp. lactis CNCM-I2494, a strain used in fermented dairy products. A chronic dinitrobenzene sulfonic acid (DNBS)-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability, and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations, and colonic cytokines were found to be altered. B. animalis ssp. lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations, and cytokine levels. Furthermore, tight junction (TJ) proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4(+) lymphocyte alterations in both spleen and mesenteric lymphoid nodes. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4(+) Th1 cells) by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5, and IL-10). Altogether, these data suggest that B. animalis ssp. lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability.
- Published
- 2016
- Full Text
- View/download PDF
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