Contributors: Da Volterra Paris, France; MetaGenoPolis; Institut National de la Recherche Agronomique (INRA); Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)); Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM); AP-HP - Hôpital Bichat - Claude Bernard Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Université Paris Diderot - Paris 7 (UPD7); Institut Gustave Roussy (IGR); Département de soins aigus Gustave Roussy (DSA); The randomized clinical trial was sponsored by Da Volterra (Paris) and funded in part by the European Union Seventh Framework Programme (FP7-HEALTH-2011-single-stage) under grant agreement number 282004, EvoTAR. Additional funding was from the Metagenopolis grant ANR-11-DPBS-0001, and from BPIFrance under the NOSOBIO collaborative program.; We thank M. Ghidi and M. N. Bouverne (Da Volterra), as well as C. Féger (Emibiothech) for coordination and management of the clinical study; E. Arcaraz, E. Desmartin, A. Toutin, T. Mezzasalma, and C. Toutin (Amatsi Group) for the development and validation of bioanalytical methods, and for performing the fecal and plasma pharmacokinetic analyses; I. Wieder and C. Bourseau for performing the phenotypic microbiological analyses; Prof A. Dufour for biopharmacological analysis; P. Clerson (Orgamétrie) for statistical analysis of the clinical data; N. Galleron and B. Quinquis (Metagenopolis) for generating sequencing data; and P. Leonard (Metagenopolis) for informatics support.; ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011); European Project: 282004,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,EVOTAR(2011)
نبذة مختصرة : MAJOR ARTICLE Clinical Trials Registration: NCT02176005 ; International audience ; Background:Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.Methods:We performed a randomized controlled trial in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added.Results:The coadministration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex vivo.Conclusions:DAV132 was highly effective to protect the gut microbiome of moxifloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.Clinical Trials Registration:NCT02176005.
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