Abstract
Broad spectrum antibiotics cause both transient and lasting damage to the ecology of the gut microbiome. Antibiotic-induced loss of gut bacterial diversity has been linked to susceptibility to enteric infections. Prior work on subtherapeutic antibiotic treatment in humans and non-human animals has suggested that entire gut communities may exhibit tolerance phenotypes. In this study, we validate the existence of these community tolerance phenotypes in the murine gut and explore how antibiotic treatment duration or a diet enriched in antimicrobial phytochemicals might influence the frequency of this phenotype. Almost a third of mice exhibited whole-community tolerance to a high dose of the β-lactam antibiotic cefoperazone, independent of antibiotic treatment duration or dietary phytochemical amendment. We observed few compositional differences between non-responder microbiota during antibiotic treatment and the untreated control microbiota. However, gene expression was vastly different between non-responder microbiota and controls during treatment, with non-responder communities showing an upregulation of antimicrobial tolerance genes, like efflux transporters, and a down-regulation of central metabolism. Future work should focus on what specific host- or microbiome-associated factors are responsible for tipping communities between responder and non-responder phenotypes so that we might learn to harness this phenomenon to protect our microbiota from routine antibiotic treatment.
Highlights
Broad spectrum antibiotics cause both transient and lasting damage to the ecology of the gut microbiome
We found that 31% (10 out of 32) of singly housed mice exposed to the same high dose of cefoperazone, which has been used to promote C. difficile colonization in prior mouse studies[33,34], were protected from antibiotic-induced ecological collapse, independent of duration or dietary treatments
We estimate that taxon abundance differences larger than twofold can be reliably detected with 5–10 samples per group using beta-binomial likelihood ratio test. 16S amplicon sequencing of the duration experiment demonstrated that most of the cefoperazone-treated mice showed altered gut microbiome communities during antibiotic treatment (Fig. 1)
Summary
Broad spectrum antibiotics cause both transient and lasting damage to the ecology of the gut microbiome. Strategies have been developed to introduce activated carbon into the lower gut during antibiotic exposure to protect colonic bacteria[22] or to use autologous fecal transplants to replenish gut diversity following treatment[23] In addition to these therapeutic strategies, the microbiome appears to exhibit natural antibiotic tolerance under certain conditions. Certain mice that received relatively high doses of cefoperazone in Schubert et al.[33] were not colonized by C. difficile following exposure These mice were not predicted to be colonized by the RF model and appeared to maintain a gut microbiome composition that was similar to the control mice
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