@article{09725e1591874636814c939aa41ad749,
title = "Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome",
abstract = "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.",
keywords = "antibiotics, diet, dysbiosis, metabolism, metagenomics, metatranscriptomics, microbiome, tolerance",
author = "Cabral, {Damien J.} and Swathi Penumutchu and Reinhart, {Elizabeth M.} and Cheng Zhang and Korry, {Benjamin J.} and Wurster, {Jenna I.} and Rachael Nilson and August Guang and Sano, {William H.} and Rowan-Nash, {Aislinn D.} and Hu Li and Peter Belenky",
note = "Funding Information: This work was supported by the U.S. Department of Defense through the Peer Reviewed Medical Research Program under award number W81XWH-18-1-0198; by the National Science Foundation through the Graduate Research Fellowship Program under award number 1644760 for D.J.C., B.J.K., S.P., and J.I.W.; and by the National Institutes of Health under institutional development awards P20GM121344 and P20GM109035 from the National Institute of General Medical Sciences , which fund the Center for Antimicrobial Resistance and Therapeutic Discovery and the COBRE Center for Computational Biology of Human Disease, respectively. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense, the National Science Foundation, or the National Institutes of Health. H.L. is supported by Glenn Foundation for Medical Research and Mayo Clinic Center for Biomedical Discovery. The Thermo Apreo VS scanning electron microscope used in this study was funded by an S10 award (NIH S10 OD023461 ) from the National Institutes of Health. Funding Information: This work was supported by the U.S. Department of Defense through the Peer Reviewed Medical Research Program under award number W81XWH-18-1-0198; by the National Science Foundation through the Graduate Research Fellowship Program under award number 1644760 for D.J.C. B.J.K. S.P. and J.I.W.; and by the National Institutes of Health under institutional development awards P20GM121344 and P20GM109035 from the National Institute of General Medical Sciences, which fund the Center for Antimicrobial Resistance and Therapeutic Discovery and the COBRE Center for Computational Biology of Human Disease, respectively. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense, the National Science Foundation, or the National Institutes of Health. H.L. is supported by Glenn Foundation for Medical Research and Mayo Clinic Center for Biomedical Discovery. The Thermo Apreo VS scanning electron microscope used in this study was funded by an S10 award (NIH S10 OD023461) from the National Institutes of Health. Conceptualization: D.J.C. and P.B. Methodology: D.J.C, P.B. and A.G. Formal Analysis: D.J.C. and C.Z. Investigation: D.J.C. B.J.K. J.I.W. R.N. W.H.S. S.P. E.M.R, P.B. and A.D.R. Data Curation: D.J.C. and P.B. Writing ? Original Draft: D.J.C. P.B. C.Z. E.M.R. B.J.K. and S.P. Writing ? Review and Editing: D.J.C. S.P. B.J.K. J.I.W. P.B. and A.D.R. Visualization: D.J.C. and C.Z. Supervision: P.B. and H.L. Funding Acquisition: P.B. and H.L. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = oct,
day = "1",
doi = "10.1016/j.cmet.2019.08.020",
language = "English (US)",
volume = "30",
pages = "800--823.e7",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}