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.

Effects of short- and long-course antibiotics on the lower intestinal microbiome as they relate to traveller’s diarrhea

“…Raymond et al studied exactly this in 18 healthy subjects, including six controls, who were administered a 7-day course of cefprozil and had their microbiome assessed using deep sequencing at 0, 7, and 90 days [22]. At baseline (day 0) the subjects were found to broadly fit into four clusters that appeared to be a variation on three previously described enterotypes [26].…”

Partial recovery of microbiomes after antibiotic treatment

“…Average change in abundance ranking between day 7 and day 0 samples for exposed participant. Only the 13 genera for which relative abundance was statistically significant between day 7 and day 0 after antibiotics treatment are displayed (p < 0.05 after Benjamini & Yekutieli false discovery rate correction, see Raymond et al 7 for details). Error bars represent confidence interval at 95%.…”

“…13 In this new analysis, we compared metagenomes using MERGEM as a filter for resistance gene k-mers, thereby measuring similarity between gut microbiomes based on sequences potentially associated with antibiotic resistance. The Jaccard similarity index calculated between day 7 and day 0 for resistance gene k-mers in participants with antibiotics (39.0%) was significantly lower than controls (64.9%) (p D 0.023, Welch Two Sample t-test) (Fig.…”

“…[4][5][6] In our recent study, we explored how a widely prescribed antibiotic, used to cure mild infections, can alter the human gut microbiome. 7 Our goal was to evaluate the impact of antibiotic treatment on the gut microbiome. To test this, we gave a 7 day course of cefprozil to 18 healthy volunteers and sequenced the microbial content of stool samples before, at the end of the 7 days course of antibiotic treatment and 90 days later.…”

Editorial Commentary: The Dawning of Microbiome Remediation for Addressing Antibiotic Resistance

“…Nearly half of these 18 antibiotic resistant threats are health care-associated pathogens and at least five frequently colonize the lower intestinal microbiota of patients. Among the many host and environmental factors that influence the composition of our microbiota, the most significant is the receipt of antibiotics [2–4]. Treatment with antibiotics eliminates not only pathogenic but also beneficial bacteria, resulting in severe disruption of the intestinal microbiota for an extended period of time (>6 months) [2].…”