Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome

Damien J. Cabral, Swathi Penumutchu, Elizabeth M. Reinhart, Cheng Zhang, Benjamin J. Korry, Jenna I. Wurster, Rachael Nilson, August Guang, William H. Sano, Aislinn D. Rowan-Nash, Hu Li, Peter Belenky

Research output: Contribution to journalArticle

4 Scopus citations


Although antibiotics disturb the structure of the gut microbiota, 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 metagenomic 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 thetaiotaomicron, which blooms in response to amoxicillin, upregulated 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. thetaiotaomicron, 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.

Original languageEnglish (US)
Pages (from-to)800-823.e7
JournalCell Metabolism
Issue number4
StatePublished - Oct 1 2019



  • antibiotics
  • diet
  • dysbiosis
  • metabolism
  • metagenomics
  • metatranscriptomics
  • microbiome
  • tolerance

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Cabral, D. J., Penumutchu, S., Reinhart, E. M., Zhang, C., Korry, B. J., Wurster, J. I., Nilson, R., Guang, A., Sano, W. H., Rowan-Nash, A. D., Li, H., & Belenky, P. (2019). Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome. Cell Metabolism, 30(4), 800-823.e7. https://doi.org/10.1016/j.cmet.2019.08.020