The initial state of the human gut microbiome determines its reshaping by antibiotics

• DOI: 10.1038/ismej.2015.148
• Publication Date: 2015-09-11T14:01:38Z
• Authors: Frédéric Raymond; Amin A Ouameur; Maxime Déraspe; Naeem Iqbal; Hélène Gingras; Bédis Dridi; Philippe Leprohon; Pier-Luc Plante; Richard Giroux; Ève Bérubé; Johanne Frenette; Dominique K Boudreau; Jean-Luc Simard; Isabelle Chabot; Marc-Christian Do...; Sylvie Trottier; Maurice Boissinot; Ann Huletsky; Paul H Roy; Marc Ouellette; Michel G Bergeron; Jacques Corbeil
• Keywords: Adult; Male; 0301 basic medicine; Bacteria; Cefprozil; 16. Peace & justice; Healthy Volunteers; Anti-Bacterial Agents; Cephalosporins; Gastrointestinal Microbiome; 3. Good health; Feces; Young Adult; 03 medical and health sciences; Bacterial Proteins; Humans; Original Article; Female; Metagenomics

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.