16 results on '"Lilia Boucinha"'
Search Results
2. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients
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Florent Malard, Anne Vekhoff, Simona Lapusan, Francoise Isnard, Evelyne D’incan-Corda, Jérôme Rey, Colombe Saillard, Xavier Thomas, Sophie Ducastelle-Lepretre, Etienne Paubelle, Marie-Virginie Larcher, Clément Rocher, Christian Recher, Suzanne Tavitian, Sarah Bertoli, Anne-Sophie Michallet, Lila Gilis, Pierre Peterlin, Patrice Chevallier, Stéphanie Nguyen, Emilie Plantamura, Lilia Boucinha, Cyrielle Gasc, Mauricette Michallet, Joel Dore, Ollivier Legrand, and Mohamad Mohty
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Science - Abstract
The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.
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- 2021
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3. Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection
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Benoît Levast, Nicolas Benech, Cyrielle Gasc, Cécile Batailler, Eric Senneville, Sébastien Lustig, Cécile Pouderoux, David Boutoille, Lilia Boucinha, Frederic-Antoine Dauchy, Valérie Zeller, Marianne Maynard, Charles Cazanave, Thanh-Thuy Le Thi, Jérôme Josse, Joël Doré, Frederic Laurent, and Tristan Ferry
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gut microbiota ,antimicrobial therapy ,antibiotics ,bone and joint infection ,dysbiosis ,Medicine (General) ,R5-920 - Abstract
There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray–Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray–Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r2 = 0.17; p < 0.0001). The PCoA analysis of the Bray–Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.
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- 2021
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4. Caecal microbiota compositions from 7-day-old chicks reared in high-performance and low-performance industrial farms and systematic culturomics to select strains with anti-Campylobacter activity.
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Aurore Duquenoy, Maryne Ania, Noémie Boucher, Frédéric Reynier, Lilia Boucinha, Christine Andreoni, and Vincent Thomas
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Medicine ,Science - Abstract
There is growing interest in exploring the chickens' intestinal microbiota and understanding its interactions with the host. The objective is to optimize this parameter in order to increase the productivity of farm animals. With the goal to isolate candidate probiotic strains, specific culturomic methods were used in our study to culture commensal bacteria from 7-days old chicks raised in two farms presenting long history of high performance. A total of 347 isolates were cultured, corresponding to at least 64 species. Among the isolates affiliated to the Firmicutes, 26 had less than 97% identity of their partial 16S sequence with that of the closest described species, while one presented less than 93% identity, thus revealing a significant potential for new species in this ecosystem. In parallel, and in order to better understand the differences between the microbiota of high-performing and low-performing animals, caecal contents of animals collected from these two farms and from a third farm with long history of low performance were collected and sequenced. This compositional analysis revealed an enrichment of Faecalibacterium-and Campylobacter-related sequences in lower-performing animals whereas there was a higher abundance of enterobacteria-related sequences in high-performing animals. We then investigated antibiosis activity against C. jejuni ATCC 700819 and C. jejuni field isolate as a first phenotypic trait to select probiotic candidates. Antibiosis was found to be limited to a few strains, including several lactic acid bacteria, a strain of Bacillus horneckiae and a strain of Escherichia coli. The antagonist activity depended on test conditions that mimicked the evolution of the intestinal environment of the chicken during its lifetime, i.e. temperature (37°C or 42°C) and oxygen levels (aerobic or anaerobic conditions). This should be taken into account according to the stage of development of the animal at which administration of the active strain is envisaged.
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- 2020
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5. An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model
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Cécile Verdier, Sylvain Denis, Cyrielle Gasc, Lilia Boucinha, Ophélie Uriot, Dominique Delmas, Joël Dore, Corentin Le Camus, Carole Schwintner, and Stéphanie Blanquet-Diot
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gut microbiota ,antibiotic ,dysbiosis ,FMT ,enema ,oral capsule ,Biology (General) ,QH301-705.5 - Abstract
Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.
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- 2021
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6. Lactobacillus paracasei feeding improves immune control of influenza infection in mice.
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Nouria Belkacem, Nicolas Serafini, Richard Wheeler, Muriel Derrien, Lilia Boucinha, Aurélie Couesnon, Nadine Cerf-Bensussan, Ivo Gomperts Boneca, James P Di Santo, Muhamed-Kkeir Taha, and Raphaëlle Bourdet-Sicard
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Medicine ,Science - Abstract
Respiratory tract infections such as flu cause severe morbidity and mortality and are among the leading causes of death in children and adults worldwide. Commensal microbiota is critical for orchestrating tissue homeostasis and immunity in the intestine. Probiotics represent an interesting source of immune modulators and several clinical studies have addressed the potential beneficial effects of probiotics against respiratory infections. Therefore, we have investigated the mechanisms of protection conferred by L. paracasei CNCM I-1518 strain in a mouse model of influenza infection. Notably, local myeloid cells accumulation is generated in the lungs after seven days feeding with L. paracasei prior to viral infection. L. paracasei-fed mice showed reduced susceptibility to the influenza infection, associated with less accumulation of inflammatory cells in the lungs, faster viral clearance and general health improvement. Interestingly, Allobaculum was significantly increased in L. paracasei-fed mice 7 days after influenza infection, even if the gut microbiota composition was not altered overall. L. paracasei-purified peptidoglycan partially recapitulated the protective phenotype observed with the entire bacteria. Collectively, our results demonstrate that oral consumption of L. paracasei CNCM I-1518 modulates lung immunity was associated with an improved control of influenza infection. These results further extend the beneficial role for certain lactobacilli to alleviate the burden of respiratory tract infections.
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- 2017
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7. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients
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Xavier Thomas, Lilia Boucinha, Christian Recher, Anne-Sophie Michallet, Sophie Ducastelle-Lepretre, Mauricette Michallet, Stéphanie Nguyen, Clément Rocher, Pierre Peterlin, Etienne Paubelle, Florent Malard, Suzanne Tavitian, Colombe Saillard, Marie-Virginie Larcher, Sarah Bertoli, Evelyne D'incan-Corda, Ollivier Legrand, Patrice Chevallier, Emilie Plantamura, Joël Doré, Anne Vekhoff, Simona Lapusan, Jerome Rey, Lila Gilis, Mohamad Mohty, Cyrielle Gasc, Françoise Isnard, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), MaaT Pharma [Lyon], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 788191,Homo.symbiosus, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Antibiotics ,General Physics and Astronomy ,Gut flora ,Feces ,0302 clinical medicine ,fluids and secretions ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,education.field_of_study ,Multidisciplinary ,biology ,Myeloid leukemia ,Fecal Microbiota Transplantation ,Middle Aged ,Anti-Bacterial Agents ,3. Good health ,Leukemia ,Treatment Outcome ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Adult ,medicine.drug_class ,Science ,Population ,Transplantation, Autologous ,digestive system ,Article ,Phase II trials ,Acute myeloid leukaemia ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,education ,Aged ,Bacteria ,business.industry ,Induction chemotherapy ,General Chemistry ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,Transplantation ,030104 developmental biology ,Immunology ,Dysbiosis ,business - Abstract
Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level., The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.
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- 2021
8. Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance in Klebsiella pneumoniae
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Lilia Boucinha, Emilie Lessoud, Lucile Pantel, Maxime Gualtieri, Anne Lanois, Emilie Racine, Alain Givaudan, Paulo Juarez, Marine Serri, Nosopharm, Smaltis SAS - R&D Department, MaaT Pharma [Lyon], Evotec ID [Lyon], Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier] (DGIMI), and Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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Pharmacology ,0303 health sciences ,biology ,030306 microbiology ,Chemistry ,Klebsiella pneumoniae ,Mutant ,ATP-binding cassette transporter ,biology.organism_classification ,Molecular biology ,Enterobacteriaceae ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,3. Good health ,03 medical and health sciences ,Response regulator ,Infectious Diseases ,Plasmid ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Pharmacology (medical) ,Bacterial outer membrane ,Gene ,030304 developmental biology - Abstract
International audience; NOSO-502 is a preclinical antibiotic candidate of the odilorhabdin class. This compound exhibits activity against Enterobacteriaceae pathogens, including carbapenemase-producing bacteria and most of the colistin (CST)-resistant strains. Among a collection of CST-resistant Klebsiella pneumoniae strains harboring mutations in the genes pmrAB , mgrB , phoPQ , and crrB , only those bearing mutations in the gene crrB were found to be resistant to NOSO-502. CrrB is a histidine kinase which acts with the response regulator CrrA to modulate the PmrAB system, which induces the restructuring of lipopolysaccharide on the outer membrane and thus leads to CST resistance. Moreover, crrB mutations also enhance the transcription of neighboring genes, such as H239_3063 , encoding an ABC transporter transmembrane region, H239_3064 , encoding a putative efflux pump also known as KexD, and H239_3065 , encoding an N -acetyltransferase. To elucidate the mechanism of resistance to NOSO-502 induced by CrrB missense mutations in K. pneumoniae , mutants of NCTC 13442 and ATCC BAA-2146 strains resistant to NOSO-502 and CST with single amino acid substitutions in CrrB (S8N, F33Y, Y34N, W140R, N141I, P151A, P151L, P151S, P151T, or F303Y) were selected. Full susceptibility to NOSO-502 was restored in crrA - or crrB -deleted K. pneumoniae NCTC 13442 CrrB (P151L) mutants, confirming the role of CrrAB in controlling this resistance pathway. Deletion of kexD (but not other neighboring genes) in the same mutant also restored NOSO-502-susceptibility. Upregulation of the kexD gene expression was observed for all CrrB mutants. Finally, plasmid expression of kexD in a K. pneumoniae strain missing the locus crrABC and kexD significantly increased resistance to NOSO-502.
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- 2021
9. Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance in
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Lucile, Pantel, Paulo, Juarez, Marine, Serri, Lilia, Boucinha, Emilie, Lessoud, Anne, Lanois, Alain, Givaudan, Emilie, Racine, and Maxime, Gualtieri
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Mechanisms of Resistance - Abstract
NOSO-502 is a preclinical antibiotic candidate of the odilorhabdin class. This compound exhibits activity against Enterobacteriaceae pathogens, including carbapenemase-producing bacteria and most of the colistin (CST)-resistant strains. Among a collection of CST-resistant Klebsiella pneumoniae strains harboring mutations in the genes pmrAB, mgrB, phoPQ, and crrB, only those bearing mutations in the gene crrB were found to be resistant to NOSO-502. CrrB is a histidine kinase which acts with the response regulator CrrA to modulate the PmrAB system, which induces the restructuring of lipopolysaccharide on the outer membrane and thus leads to CST resistance. Moreover, crrB mutations also enhance the transcription of neighboring genes, such as H239_3063, encoding an ABC transporter transmembrane region, H239_3064, encoding a putative efflux pump also known as KexD, and H239_3065, encoding an N-acetyltransferase. To elucidate the mechanism of resistance to NOSO-502 induced by CrrB missense mutations in K. pneumoniae, mutants of NCTC 13442 and ATCC BAA-2146 strains resistant to NOSO-502 and CST with single amino acid substitutions in CrrB (S8N, F33Y, Y34N, W140R, N141I, P151A, P151L, P151S, P151T, or F303Y) were selected. Full susceptibility to NOSO-502 was restored in crrA- or crrB-deleted K. pneumoniae NCTC 13442 CrrB (P151L) mutants, confirming the role of CrrAB in controlling this resistance pathway. Deletion of kexD (but not other neighboring genes) in the same mutant also restored NOSO-502-susceptibility. Upregulation of the kexD gene expression was observed for all CrrB mutants. Finally, plasmid expression of kexD in a K. pneumoniae strain missing the locus crrABC and kexD significantly increased resistance to NOSO-502.
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- 2021
10. A comprehensive evaluation of binning methods to recover human gut microbial species from a non-redundant reference gene catalog
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Marianne Borderes, Lilia Boucinha, Susana Vinga, Cyrielle Gasc, Marie-France Sagot, Mariana Galvão Ferrarini, Emmanuel Prestat, Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), MaaT Pharma [Lyon], Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), Evotec ID [Lyon], and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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AcademicSubjects/SCI01140 ,0303 health sciences ,AcademicSubjects/SCI01060 ,Relation (database) ,Computer science ,[SDV]Life Sciences [q-bio] ,AcademicSubjects/SCI00030 ,No reference ,Computational biology ,AcademicSubjects/SCI01180 ,Methart ,Set (abstract data type) ,03 medical and health sciences ,0302 clinical medicine ,Human gut ,Metagenomics ,Scalability ,Reference gene ,AcademicSubjects/SCI00980 ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Cluster analysis ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
The human gut microbiota performs functions that are essential for the maintenance of the host physiology. However, characterizing the functioning of microbial communities in relation to the host remains challenging in reference-based metagenomic analyses. Indeed, as taxonomic and functional analyses are performed independently, the link between genes and species remains unclear. Although a first set of species-level bins was built by clustering co-abundant genes, no reference bin set is established on the most used gut microbiota catalog, the Integrated Gene Catalog (IGC). With the aim to identify the best suitable method to group the IGC genes, we benchmarked nine taxonomy-independent binners implementing abundance-based, hybrid and integrative approaches. To this purpose, we designed a simulated non-redundant gene catalog (SGC) and computed adapted assessment metrics. Overall, the best trade-off between the main metrics is reached by an integrative binner. For each approach, we then compared the results of the best-performing binner with our expected community structures and applied the method to the IGC. The three approaches are distinguished by specific advantages, and by inherent or scalability limitations. Hybrid and integrative binners show promising and potentially complementary results but require improvements to be used on the IGC to recover human gut microbial species.
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- 2021
11. A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes
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Jennifer Yansouni, Filipe De Vadder, Martin Schwarzer, Dagmar Šrůtková, Ana Delgado, Alban Mathieu, Anne-Laure Bulteau, François Leulier, Andrei Bunescu, Céline Elie, Severine Planel, Bärbel Stecher, Lilia Boucinha, Djomangan Adama Ouattara, Céline Couturier, Andrea Tamellini, Tereza Novotná, Marion Darnaud, Adrien Saliou, Pascaline Bogeat, Helene Dugua, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BIOASTER Microbiology Technology Institute [Lyon], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute of Microbiology of the Czech Academy of Sciences [Prague, Czech Republic] (MBU / CAS), Czech Academy of Sciences [Prague] (CAS), Ludwig-Maximilians University [Munich] (LMU), German Center for Infection Research, Partnersite Munich (DZIF), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Leulier, François
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Male ,Physiology ,Science ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Computational biology ,Gut flora ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,Article ,Feces ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,[SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology ,Animals ,Germ-Free Life ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,030304 developmental biology ,Genetics ,2. Zero hunger ,0303 health sciences ,Multidisciplinary ,Bacteria ,Whole Genome Sequencing ,biology ,030302 biochemistry & molecular biology ,Body Weight ,Laboratory mouse ,Robustness (evolution) ,General Chemistry ,Fecal microbiota ,biology.organism_classification ,Confounding effect ,Phenotype ,Gut microbiome ,Gastrointestinal Microbiome ,Specific Pathogen-Free Organisms ,Mice, Inbred C57BL ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Metagenomics ,[SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology ,Female ,Microbiome ,030217 neurology & neurosurgery ,Microbiota composition - Abstract
Mus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, here we report the development of a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and the derivation of a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. In this work, we show that the GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers opportunities for research focused on how the microbiota shapes host physiology in health and disease., Here, the authors develop and characterize a mouse microbiota composed of 15 strains representative of the intestinal microbiota found in C57BL/6J specific opportunistic- and pathogen-free (C57Bl/6J SOPF) mice and derive a new standardized gnotobiotic mouse model, called GM15, which recapitulates the phenotypes of SOPF or SPF animals in different animal facilities with improved reproducibility.
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- 2019
12. An oral FMT capsule as efficient as an enema for microbiota reconstruction following disruption by antibiotics, as assessed in an in vitro human gut model.
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Cécile, Verdier, primary, Sylvain, Denis, additional, Cyrielle, Gasc, additional, Lilia, Boucinha, additional, Ophélie, Uriot, additional, Dominique, Delmas, additional, Joël, Dore, additional, Corentin, Le Camus, additional, Carole, Schwintner, additional, and Blanquet-Doit, Stephanie, additional
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- 2020
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13. The odyssee study: prevention of dysbiosis complications with autologous fecal microbiota transfer (fmt) in acute myeloid leukemia (aml) patients undergoing intensive treatment: results of a prospective multicenter trial
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Joël Doré, Mauricette Michallet, Simona Lapusan, Florent Malard, Patrice Chevallier, Sophie Ducastelle-Lepretre, Suzanne Tavitian, Colombe Saillard, Stephanie Nguyen-Quoc, Xavier Thomas, Emilie Plantamura, Pierre Peterlin, Clément Rocher, Lilia Boucinha, Anne Vekhoff, Françoise Huguet, Ollivier Legrand, Evelyne D'Incan, Anne-Sophie Michallet, Christian Recher, Etienne Paubelle, Cyrielle Gasc, Jerome Rey, Lila Gilis, Mohamad Mohty, Françoise Isnard, Marie Virginie Larcher, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Service d'hématologie, Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MaaT Pharma [Lyon], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MaaT Pharma, and American Society of Hematology (ASH). USA.
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0301 basic medicine ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Immunology ,Population ,Biochemistry ,law.invention ,03 medical and health sciences ,Randomized controlled trial ,law ,Internal medicine ,Multicenter trial ,medicine ,Clinical endpoint ,education ,Adverse effect ,ComputingMilieux_MISCELLANEOUS ,education.field_of_study ,business.industry ,Induction chemotherapy ,Cell Biology ,Hematology ,medicine.disease ,Chemotherapy regimen ,3. Good health ,030104 developmental biology ,business ,Dysbiosis - Abstract
Introduction. AML standard intensive induction chemotherapy ("3+7" or equivalent) combined with wide spectrum antibiotics can dramatically alter the composition of the gut microbiota, leading to dysbiosis which is characterized by loss of microbial diversity. Such dysbiosis status can promote a pathological condition involving uncontrolled local immune responses, systemic inflammation and increased incidence of adverse events. The development of FMT-based drugs to restore microbial communities could offer novel therapeutic possibilities to reduce such adverse events and potentially improve outcomes in AML. We therefore conducted this single arm prospective phase I/II multicenter trial (NCT02928523) to evaluate the use of a FMT-based drug in association with AML induction treatment to restore the gut microbiota diversity. Patients and methods. A total of 62 consecutive patients aged between 24 and 69 years old with a diagnosis of de novo AML were screened in 7 French sites. At time of admission and AML diagnosis (Step 1=S1), patients' faeces were collected, rigorously screened, prepared following a standardized process, and stored at -80°C until later administration. The drug was administered as an enema after hematopoietic recovery (S2) and before consolidation chemotherapy (Conso). The primary endpoint was the recovery of at least 70% of microbiota diversity (based on the Simpson index) after drug administration and the reduction of multidrug resistant bacteria carriage. Blood and feces samples were collected at S1, S2, and around 10 days post-FMT before Conso (S3). Microbiome diversity restoration was assessed by metagenomics analysis through Illumina HiSeq shotgun sequencing. Antibiotic resistance gene carriage (ARGC, also known as resistome) was evaluated through mapping of readouts on the MEGARES database. Secondary objectives included safety and analysis of host response with assessment of blood and fecal markers by ELISA and Luminex. Results. Overall, 25 patients were actually treated with FMT, and 20 were included in the per-protocol population. Induction Chemotherapy (IC) induced a dramatic shift in microbial communities, with a significant 42.3% decrease of mean α-diversity Simpson index between S1 and S2 at species level (0.85 to 0.50; p No serious adverse events (SAE) were observed within 30 days after FMT and all post FMT SAEs were not related to the FMT procedure. Moreover, FMT did not induce any local or systemic inflammatory reaction as measured by fecal and blood markers (fecal neopterin and IgA; plasmatic CRP, IL-6 and sCD14). Interestingly, restoration of the microbiome diversity was associated with a significant reduction of CRP and fecal neopterin levels, suggesting a potential anti-inflammatory impact of FMT. Overall, FMT was well tolerated and had an excellent safety profile. The one-year overall survival estimate in the whole cohort was 84% (4 deaths among 25, none of which were related to FMT: 2 multiple organ failures, 1 heart attack and 1 grade IV resistant GVHD). The median time to death from the second FMT was 182.5 days (113-225 days). Conclusions. This is the first prospective trial testing the safety and efficacy of FMT in AML patients receiving intensive induction chemotherapy. The trial achieved its primary endpoint and established the capacity of FMT to restore a diverse microbiome with high levels of similarity to baseline, as well as reducing ARGC and intestinal inflammation. A controlled randomized trial with repeated FMT administrations is currently planned to further evaluate the impact of FMT on clinical outcomes and long-term survival. (This trial was funded by MaaT Pharma whose product was tested in this protocol). Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria. Doré:MaaT Pharma: Consultancy, Honoraria.
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- 2018
14. MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype
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Elsa Kress, Mathias Heikenwalder, Gerard Lina, David Bauché, Saskia Lippens, Claire Macari, Marie-Cécile Michallet, Mathias Chamaillard, Sophia Djebali, Emilie Plantamura, Lyvia Moudombi, Jacqueline Marvel, Christophe Caux, Julien C. Marie, Annabelle Cesaro, Lilia Boucinha, Amiran Dzutsev, Jean-Philippe Rasigade, Ulrike Rothermel, Giorgio Trinchieri, Azzak Bentaher-Belaaouaj, Oana Dumitrescu, Morgan Grau, Michelina Plateroti, Clovis Bondu, Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancer Inflammation Program [Frederick], Center for Cancer Research, Leidos Biomedical Research, Inc [Frederick, MD, USA], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], We acknowledge the contributions of the Structure Fédérative de Recherche BioSciences Gerland-Lyon Sud (UMS3444/US8-Ecole Normale Superieure de Lyon, Universite Claude Bernard de Lyon CNRS, INSERM) facilities, especially AniRA ImmOS. This work was supported by Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Lyon I, Hospices Civils de Lyon, Association 'ARCHE,' and Agence Nationale de la Recherche Grant ANR-11-RPIB-0019-03 (to J.M.), a grant from the Département du Rhône-Fonds Européen de Développement Régional (PLATINE) (J.M.), and European Commission Grant LSHG-CT-2006-037188, The European Mouse Disease Clinic (to J.M.)., We thank J. Tschopp’s laboratory for Cardif (MAVS-deficient) mice, Martine Tomkowiak, Julien Mafille, and Barbara Gilbert for expert technical assistance, Anca Hennino for confocal images, Christophe Arpin and Mohamad Sobh for statistical data analysis, Bertrand Dubois, Marc Vocanson, and Jean-François Nicolas for helpful discussions on the DTH model, Thierry Walzer, Laurent Genestier, Bertrand Dubois, and Gérard Eberl for critical reading of the manuscript, Bariza Blanquier for help with qPCR analysis (genetic analysis), Thibault Andrieu and Sébastien Dussurgey (AniRA-Cytometry), Olga Azocar and Christophe Chamot from the Plateau Technique Imagerie/Microcopie, and the staff of AniRA-PBES, especially Jean-Louis Thoumas and Céline Angleraux., Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MICHALLET, MARIE-CECILE
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0301 basic medicine ,MESH: Signal Transduction ,RIG-like receptors ,MESH: Intestines/immunology ,MESH: Skin Diseases, Bacterial/pathology ,Gut flora ,MESH: Skin Diseases, Bacterial/metabolism ,MESH: Mice, Knockout ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Mice ,0302 clinical medicine ,MESH: Animals ,MESH: Hypersensitivity/metabolism ,[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology ,Sensitization ,Mice, Knockout ,Multidisciplinary ,integumentary system ,dysbiosis ,Biological Sciences ,MAVS ,Phenotype ,3. Good health ,Intestines ,medicine.anatomical_structure ,MESH: Intestines/pathology ,030220 oncology & carcinogenesis ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,[SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology ,Signal Transduction ,MESH: Intestines/microbiology ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Dysbiosis/complications ,Biology ,MESH: Gastrointestinal Microbiome/immunology ,MESH: Phenotype ,digestive system ,03 medical and health sciences ,MESH: Skin Diseases, Bacterial/etiology ,MESH: Hypersensitivity/etiology ,Immunity ,MESH: Mice, Inbred C57BL ,MESH: Homeodomain Proteins/metabolism ,medicine ,Hypersensitivity ,allergic skin pathologies ,MESH: Hypersensitivity/pathology ,Animals ,Colitis ,Allergic contact dermatitis ,[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity ,MESH: Mice ,Adaptor Proteins, Signal Transducing ,Homeodomain Proteins ,MESH: Adaptor Proteins, Signal Transducing/physiology ,Intestinal permeability ,Skin Diseases, Bacterial ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Immunology ,MESH: Homeodomain Proteins/genetics ,MESH: Disease Models, Animal ,Dysbiosis ,MESH: Female - Abstract
International audience; Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs -/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.
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- 2018
15. Caecal microbiota compositions from 7-day-old chicks reared in high-performance and low-performance industrial farms and systematic culturomics to select strains with anti-Campylobacter activity
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Maryne Ania, Aurore Duquenoy, Christine Andreoni, Vincent Thomas, Lilia Boucinha, Noémie Boucher, and Frédéric Reynier
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Aging ,Veterinary medicine ,Cell Culture Techniques ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Biochemistry ,Poultry ,law.invention ,Probiotic ,Antibiotics ,law ,Campylobacter Jejuni ,Ruminococcus ,Campylobacter Infections ,Medicine and Health Sciences ,Gamefowl ,Cecum ,0303 health sciences ,Multidisciplinary ,biology ,Antimicrobials ,Campylobacter ,Eukaryota ,Drugs ,Agriculture ,Bacterial Pathogens ,Nucleic acids ,Ribosomal RNA ,Medical Microbiology ,Vertebrates ,Medicine ,Anaerobic bacteria ,Pathogens ,Research Article ,Cell biology ,Cellular structures and organelles ,Farms ,Firmicutes ,Science ,Anaerobic Bacteria ,Microbiology ,Campylobacter jejuni ,Birds ,03 medical and health sciences ,Microbial Control ,medicine ,Animals ,Non-coding RNA ,Microbial Pathogens ,Escherichia coli ,Poultry Diseases ,030304 developmental biology ,Pharmacology ,Bacteria ,030306 microbiology ,Gut Bacteria ,Antibiosis ,Organisms ,Biology and Life Sciences ,biology.organism_classification ,Gastrointestinal Microbiome ,Fowl ,Amniotes ,RNA ,Chickens ,Zoology ,Ribosomes - Abstract
There is growing interest in exploring the chickens' intestinal microbiota and understanding its interactions with the host. The objective is to optimize this parameter in order to increase the productivity of farm animals. With the goal to isolate candidate probiotic strains, specific culturomic methods were used in our study to culture commensal bacteria from 7-days old chicks raised in two farms presenting long history of high performance. A total of 347 isolates were cultured, corresponding to at least 64 species. Among the isolates affiliated to the Firmicutes, 26 had less than 97% identity of their partial 16S sequence with that of the closest described species, while one presented less than 93% identity, thus revealing a significant potential for new species in this ecosystem. In parallel, and in order to better understand the differences between the microbiota of high-performing and low-performing animals, caecal contents of animals collected from these two farms and from a third farm with long history of low performance were collected and sequenced. This compositional analysis revealed an enrichment of Faecalibacterium-and Campylobacter-related sequences in lower-performing animals whereas there was a higher abundance of enterobacteria-related sequences in high-performing animals. We then investigated antibiosis activity against C. jejuni ATCC 700819 and C. jejuni field isolate as a first phenotypic trait to select probiotic candidates. Antibiosis was found to be limited to a few strains, including several lactic acid bacteria, a strain of Bacillus horneckiae and a strain of Escherichia coli. The antagonist activity depended on test conditions that mimicked the evolution of the intestinal environment of the chicken during its lifetime, i.e. temperature (37°C or 42°C) and oxygen levels (aerobic or anaerobic conditions). This should be taken into account according to the stage of development of the animal at which administration of the active strain is envisaged.
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- 2020
16. Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny
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Fabien, Crauste, Julien, Mafille, Lilia, Boucinha, Sophia, Djebali, Olivier, Gandrillon, Jacqueline, Marvel, and Christophe, Arpin
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B-Lymphocyte Subsets ,Cell Differentiation ,CD8-Positive T-Lymphocytes ,Models, Theoretical ,Lymphocyte Activation ,Cell Line ,Mice, Inbred C57BL ,Mice ,Ki-67 Antigen ,Phenotype ,Biological Ontologies ,Proto-Oncogene Proteins c-bcl-2 ,Animals ,Immunologic Memory - Abstract
Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway. Moreover, our mathematical model allows long-term prediction of memory cell numbers from a few early experimental measurements. Our work thus provides a phenotypic means to identify effector and memory cells, as well as a mathematical framework to investigate their genealogy and to predict the outcome of immunization regimens in terms of memory cell numbers generated.
- Published
- 2016
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