Although antibiotics disturb the structure of the gut mi-crobiota, factors that modulate these perturbations are poorly understood. Bacterial metabolism is an important regulator of susceptibility in vitro and likely plays a large role within the host. We applied a metage-nomic and metatranscriptomic approach to link antibiotic-induced taxonomic and transcriptional responses within the murine microbiome. We found that antibiotics significantly alter the expression of key metabolic pathways at the whole-community and single-species levels. Notably, Bacteroides thetaiotaomi-cron, which blooms in response to amoxicillin, upregu-lated polysaccharide utilization. In vitro, we found that the sensitivity of this bacterium to amoxicillin was elevated by glucose and reduced by polysaccharides. Accordingly, we observed that dietary composition affected the abundance and expansion of B. thetaio-taomicron, as well as the extent of microbiome disruption with amoxicillin. Our work indicates that the metabolic environment of the microbiome plays a role in the response of this community to antibiotics.
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