title: The initial state of the human gut microbiome determines its reshaping by antibiotics.
abstract: Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments.
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Raymond
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Amin A
authors.initials: AA
authors.lastname: Ouameur
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Déraspe
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Naeem
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gingras
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Bédis
authors.initials: B
authors.lastname: Dridi
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Leprohon
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Pier-Luc
authors.initials: PL
authors.lastname: Plante
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Giroux
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Ève
authors.initials: È
authors.lastname: Bérubé
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Frenette
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Dominique K
authors.initials: DK
authors.lastname: Boudreau
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Simard
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chabot
authors.affiliation: Institut National de Santé Publique du Québec, Laboratoire de Santé Publique du Québec, Montréal, Québec, Canada.
authors.forename: Marc-Christian
authors.initials: MC
authors.lastname: Domingo
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Trottier
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Maurice
authors.initials: M
authors.lastname: Boissinot
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Ann
authors.initials: A
authors.lastname: Huletsky
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Roy
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ouellette
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Bergeron
authors.affiliation: Centre de Recherche en Infectiologie, CHU de Québec-Université Laval, Québec, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Corbeil
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002511:Cephalosporins / Q000008:administration & dosage; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D056186:Metagenomics; D055815:Young Adult; D000097670:Cefprozil
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D000097670:Cefprozil