Perturbation and resilience of the gut microbiome up to 3 months after β-lactams exposure in healthy volunteers suggest an important role of microbial β-lactamases
2024
D’humières, Camille | Delavy, Margot | Alla, Laurie | Ichou, Farid | Gauliard, Emilie | Ghozlane, Amine | Levenez, Florence | Galleron, Nathalie | Quinquis, Benoit | Pons, Nicolas | Mullaert, Jimmy | Bridier-Nahmias, Antoine | Condamine, Bénédicte | Touchon, Marie | Rainteau, Dominique | Lamazière, Antonin | Lesnik, Philippe | Ponnaiah, Maharajah | Lhomme, Marie | Sertour, Natacha | Devente, Savannah | Docquier, Jean-Denis | Bougnoux, Marie-Elisabeth | Tenaillon, Olivier | Magnan, Mélanie | Ruppé, Etienne | Grall, Nathalie | Duval, Xavier | Ehrlich, Dusko | Mentré, France | Denamur, Erick | Rocha, Eduardo, P C | Le Chatelier, Emmanuelle | Burdet, Charles | Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord | Génomique évolutive des Microbes / Microbial Evolutionary Genomics ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF) ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | MetaGenoPolis (MGP (US 1367)) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN) ; CHU Pitié-Salpêtrière [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) | 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) | Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité) | CIC Hôpital Bichat ; AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine | Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN) ; CHU Pitié-Salpêtrière [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)-CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Università degli Studi di Siena = University of Siena (UNISI) | Unité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris] ; Assistance Publique - Hôpitaux de Paris | Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425) ; AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | University College of London [London] (UCL) | ANR-16-CE15-0022,PREDIRES,PREDIction de l'émergence de la RESistance bactérienne dans le microbiote intestinal humain lors d'un traitement antibiotique(2016) | ANR-14-IFEC-0004,FunComPath,From fungal commensalism to pathogenicity:dissection of the colonization-to-infection shift of Candida albicans(2014) | ANR-10-INBS-0009,France Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010) | ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011)
International audience
Afficher plus [+] Moins [-]anglais. Background Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. Results While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. Conclusions In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon.
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