Pulsed antibiotic treatments of gnotobiotic mice manifest in complex bacterial community dynamics and resistance effects

Bacteria can evolve to withstand a wide range of antibiotics (ABs) by using various resistance mechanisms. How ABs affect the ecology of the gut microbiome is still poorly understood. We investigated strain-specific responses and evolution during repeated AB perturbations by three clinically relevant ABs, using gnotobiotic mice colonized with a synthetic bacterial community (oligo-mouse-microbiota). Over 80 days, we observed resilience effects at the strain and community levels, and we found that they were correlated with modulations of the estimated growth rate and levels of prophage induction as determined from metagenomics data. Moreover, we tracked mutational changes in the bacterial populations, and this uncovered clonal expansion and contraction of haplotypes and selection of putative AB resistance-conferring SNPs. We functionally verified these mutations via reisolation of clones with increased minimum inhibitory concentration (MIC) of ciprofloxacin and tetracycline from evolved communities. This demonstrates that host-associated microbial communities employ various mechanisms to respond to selective pressures that maintain community stability. [Display omitted] •Pulsed antibiotic treatment leads to resilience effects in the bacterial community•Antibiotic therapy alters prophage activity and bacterial growth rates•Detection of bacterial single-nucleotide variants is linked to antibiotic resistance•Reisolation of evolved bacteria confirms increased resistance to antibiotics Münch et al. explore the impact of repeated antibiotic treatments on gut microbiome stability in gnotobiotic mice. The study reveals complex community dynamics, strain-specific adaptations, altered growth rates, and changes in prophage activity, demonstrating that host-associated microbial communities use diverse strategies to maintain stability under selective pressures.