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Impact d'une antibiothérapie sur le microbiote intestinal

Author: Charles BurdetFrance MentréOlivier TenaillonJean-Luc MainardiDidier GuillemotAll authors
Publisher: 2018.
Dissertation: Thèse de doctorat : Santé publique. Epidémiologie clinique : Sorbonne Paris Cité : 2018.
Edition/Format:   Computer file : Document : Thesis/dissertation : French
Summary:
Le développement des méthodes de séquençage de nouvelle génération a permis d'approfondir les connaissances sur le rôle des communautés bactériennes commensales pour la santé de leur hôte, et l'impact négatif de la perturbation de leur équilibre. Les antibiotiques sont les principaux perturbateurs de cet équilibre, mais leur impact n'a pas été quantifié précisément.Nous avons quantifié la
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Genre/Form: Thèses et écrits académiques
Material Type: Document, Thesis/dissertation, Internet resource
Document Type: Internet Resource, Computer File
All Authors / Contributors: Charles Burdet; France Mentré; Olivier Tenaillon; Jean-Luc Mainardi; Didier Guillemot; Marie-Cécile Ploy; Lulla Opatowski-Mezrahi; Daniel Vittecoq; Université Sorbonne Paris Cité.; École doctorale Pierre Louis de santé publique : épidémiologie et sciences de l'information biomédicale (Paris / 2000-....).; Université Paris Diderot - Paris 7 (1970-2019).; Infection, anti-microbien, modélisation, évolution (Paris).
OCLC Number: 1105983904
Notes: Titre provenant de l'écran-titre.
Description: 1 online resource
Responsibility: Charles Burdet ; sous la direction de France Mentré.

Abstract:

Le développement des méthodes de séquençage de nouvelle génération a permis d'approfondir les connaissances sur le rôle des communautés bactériennes commensales pour la santé de leur hôte, et l'impact négatif de la perturbation de leur équilibre. Les antibiotiques sont les principaux perturbateurs de cet équilibre, mais leur impact n'a pas été quantifié précisément.Nous avons quantifié la relation entre les concentrations fécales d'antibiotiques et la perturbation de la diversité bactérienne au sein du microbiote intestinal, et modélisé le lien entre la perte de diversité bactérienne et la probabilité de décès dans un modèle animal de colite à Clostridium difficile induite par les antibiotiques. Nous avons montré que l'indice de diversité de Shannon et la distance UniFac non pondérée étaient les indices de diversité qui étaient le plus prédictif du décès dans ce modèle d'infection.Chez des volontaires sains, nous avons développé un modèle mathématique semimécanistique de l'évolution de la diversité au sein du microbiote, mesurée par deux indices de diversité, après perturbation antibiotique, et quantifié la relation entre l'exposition individuelle plasmatique et fécale à un antibiotique, et son effet sur la perturbation de la diversité bactérienne au cours du temps. Nous avons également analysé le rôle de la voie d'élimination des antibiotiques pour la limitation de l'impact d'un antibiotique sur le microbiote. Ces travaux nous ont permis de montrer que le microbiote intestinal présente une grande sensibilité aux antibiotiques, et que la voie d'élimination ne semble de ce fait pas jouer un rôle prépondérant dans la perspective de limiter l'impact des antibiotiques sur le microbiote intestinal.

The development of next generation sequencing broadened our knowledge on the role of commensal bacterial communities on their host's health, and the negative impact of their disruption. Antibiotics are the main disrupting factor, but their impact has not been precisely quantified.We quantified the relationship between antibiotic fecal concentrations and the loss of bacterial diversity in the intestinal microbiota, and modelled the link between the loss of diversity and mortality in a hamster model of antibiotic-induced Clostridium difficile infection. We showed that the Shannon diversity index and the unweighted UniFrac distance are the 2 indices that best predict mortality in this model. In healthy volunteers, we developed a semi-mechanistic model of the evolution over time of bacterial diversity - measured by two indices - after an antibiotic perturbation, and quantified the relationship between antibiotic concentrations in plasma and feces and the loss of bacterial diversity in the intestinal microbiota. We also analyzed the role of the antibiotic elimination pathway in the reduction of their impact on the microbiota. In this work, we showed that the intestinal microbiota is highly susceptible to antibiotics, and that the elimination route doesn't have a major role, in the perspective of limiting antibiotics' impact on the intestinal microbiota.

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Les antibiotiques sont les principaux perturbateurs de cet \u00E9quilibre, mais leur impact n\'a pas \u00E9t\u00E9 quantifi\u00E9 pr\u00E9cis\u00E9ment.Nous avons quantifi\u00E9 la relation entre les concentrations f\u00E9cales d\'antibiotiques et la perturbation de la diversit\u00E9 bact\u00E9rienne au sein du microbiote intestinal, et mod\u00E9lis\u00E9 le lien entre la perte de diversit\u00E9 bact\u00E9rienne et la probabilit\u00E9 de d\u00E9c\u00E8s dans un mod\u00E8le animal de colite \u00E0 Clostridium difficile induite par les antibiotiques. Nous avons montr\u00E9 que l\'indice de diversit\u00E9 de Shannon et la distance UniFac non pond\u00E9r\u00E9e \u00E9taient les indices de diversit\u00E9 qui \u00E9taient le plus pr\u00E9dictif du d\u00E9c\u00E8s dans ce mod\u00E8le d\'infection.Chez des volontaires sains, nous avons d\u00E9velopp\u00E9 un mod\u00E8le math\u00E9matique semim\u00E9canistique de l\'\u00E9volution de la diversit\u00E9 au sein du microbiote, mesur\u00E9e par deux indices de diversit\u00E9, apr\u00E8s perturbation antibiotique, et quantifi\u00E9 la relation entre l\'exposition individuelle plasmatique et f\u00E9cale \u00E0 un antibiotique, et son effet sur la perturbation de la diversit\u00E9 bact\u00E9rienne au cours du temps. Nous avons \u00E9galement analys\u00E9 le r\u00F4le de la voie d\'\u00E9limination des antibiotiques pour la limitation de l\'impact d\'un antibiotique sur le microbiote. Ces travaux nous ont permis de montrer que le microbiote intestinal pr\u00E9sente une grande sensibilit\u00E9 aux antibiotiques, et que la voie d\'\u00E9limination ne semble de ce fait pas jouer un r\u00F4le pr\u00E9pond\u00E9rant dans la perspective de limiter l\'impact des antibiotiques sur le microbiote intestinal.<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\nschema:exampleOfWork<\/a> <http:\/\/worldcat.org\/entity\/work\/id\/9360244900<\/a>> ;\u00A0\u00A0\u00A0\nschema:genre<\/a> \"Th\u00E8ses et \u00E9crits acad\u00E9miques<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\nschema:inLanguage<\/a> \"fr<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Impact d\'une antibioth\u00E9rapie sur le microbiote intestinal<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\nschema:productID<\/a> \"1105983904<\/span>\" ;\u00A0\u00A0\u00A0\nschema:url<\/a> <https:\/\/tel.archives-ouvertes.fr\/tel-02167851<\/a>> ;\u00A0\u00A0\u00A0\nschema:url<\/a> <http:\/\/www.theses.fr\/2018USPCC058\/document<\/a>> ;\u00A0\u00A0\u00A0\nschema:url<\/a> <http:\/\/theses.md.univ-paris-diderot.fr\/BURDET_Charles_2_complete_20180612.pdf<\/a>> ;\u00A0\u00A0\u00A0\nwdrs:describedby<\/a> <http:\/\/www.worldcat.org\/title\/-\/oclc\/1105983904<\/a>> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n\n

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<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Organization\/ecole_doctorale_pierre_louis_de_sante_publique_epidemiologie_et_sciences_de_l_information_biomedicale_paris_2000<\/a>> # \u00C9cole doctorale Pierre Louis de sant\u00E9 publique : \u00E9pid\u00E9miologie et sciences de l\'information biom\u00E9dicale (Paris \/ 2000-....).<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Organization<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"\u00C9cole doctorale Pierre Louis de sant\u00E9 publique : \u00E9pid\u00E9miologie et sciences de l\'information biom\u00E9dicale (Paris \/ 2000-....).<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Organization\/infection_anti_microbien_modelisation_evolution_paris<\/a>> # Infection, anti-microbien, mod\u00E9lisation, \u00E9volution (Paris).<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Organization<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Infection, anti-microbien, mod\u00E9lisation, \u00E9volution (Paris).<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Organization\/universite_paris_diderot_paris_7_1970_2019<\/a>> # Universit\u00E9 Paris Diderot - Paris 7 (1970-2019).<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Organization<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Universit\u00E9 Paris Diderot - Paris 7 (1970-2019).<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Organization\/universite_sorbonne_paris_cite<\/a>> # Universit\u00E9 Sorbonne Paris Cit\u00E9.<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Organization<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Universit\u00E9 Sorbonne Paris Cit\u00E9.<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/burdet_charles<\/a>> # Charles Burdet<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Burdet<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Charles<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Charles Burdet<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/guillemot_didier<\/a>> # Didier Guillemot<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Guillemot<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Didier<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Didier Guillemot<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/mainardi_jean_luc<\/a>> # Jean-Luc Mainardi<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Mainardi<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Jean-Luc<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Jean-Luc Mainardi<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/mentre_france<\/a>> # France Mentr\u00E9<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Mentr\u00E9<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"France<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"France Mentr\u00E9<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/opatowski_mezrahi_lulla_1979<\/a>> # Lulla Opatowski-Mezrahi<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:birthDate<\/a> \"1979<\/span>\" ;\u00A0\u00A0\u00A0\nschema:deathDate<\/a> \"\" ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Opatowski-Mezrahi<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Lulla<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Lulla Opatowski-Mezrahi<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/ploy_marie_cecile<\/a>> # Marie-C\u00E9cile Ploy<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Ploy<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Marie-C\u00E9cile<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Marie-C\u00E9cile Ploy<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/tenaillon_olivier<\/a>> # Olivier Tenaillon<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Tenaillon<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Olivier<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Olivier Tenaillon<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Person\/vittecoq_daniel<\/a>> # Daniel Vittecoq<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Person<\/a> ;\u00A0\u00A0\u00A0\nschema:familyName<\/a> \"Vittecoq<\/span>\" ;\u00A0\u00A0\u00A0\nschema:givenName<\/a> \"Daniel<\/span>\" ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Daniel Vittecoq<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Thing\/modelisation_non_lineaire_a_effets_mixtes<\/a>> # Mod\u00E9lisation non lin\u00E9aire \u00E0 effets mixtes<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Thing<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Mod\u00E9lisation non lin\u00E9aire \u00E0 effets mixtes<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/antibiotiques<\/a>> # Antibiotiques<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Antibiotiques<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/clostridium_difficile<\/a>> # Clostridium difficile<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Clostridium difficile<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/dysbiose<\/a>> # Dysbiose<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Dysbiose<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/flore_intestinale_effets_des_medicaments<\/a>> # Flore intestinale--Effets des m\u00E9dicaments<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Flore intestinale--Effets des m\u00E9dicaments<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/metagenomique<\/a>> # M\u00E9tag\u00E9nomique<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"M\u00E9tag\u00E9nomique<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/pharmacocinetique<\/a>> # Pharmacocin\u00E9tique<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Pharmacocin\u00E9tique<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/pharmacodynamie<\/a>> # Pharmacodynamie<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"Pharmacodynamie<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/experiment.worldcat.org\/entity\/work\/data\/9360244900#Topic\/resistance_aux_antibiotiques<\/a>> # R\u00E9sistance aux antibiotiques<\/span>\n\u00A0\u00A0\u00A0\u00A0a \nschema:Intangible<\/a> ;\u00A0\u00A0\u00A0\nschema:name<\/a> \"R\u00E9sistance aux antibiotiques<\/span>\"@fr<\/a> ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/id.loc.gov\/vocabulary\/countries\/fr<\/a>>\u00A0\u00A0\u00A0\u00A0a \nschema:Place<\/a> ;\u00A0\u00A0\u00A0\ndcterms:identifier<\/a> \"fr<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n
<http:\/\/www.theses.fr\/2018USPCC058\/document<\/a>>\u00A0\u00A0\u00A0\nrdfs:comment<\/a> \"Acc\u00E8s au texte int\u00E9gral<\/span>\" ;\u00A0\u00A0\u00A0\u00A0.\n\n\n<\/div>\n