Letter | Published:

Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion

Nature volume 534, pages 697699 (30 June 2016) | Download Citation

Abstract

Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars1, increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse2,3. These antibiotic-induced changes in the gut microbiota can be studied in mice, in which the disruption of a balanced microbial community by treatment with the antibiotic streptomycin leads to an expansion of S. enterica serovars in the large bowel4. However, the mechanisms by which streptomycin treatment drives an expansion of S. enterica serovars are not fully resolved. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovar Typhimurium (S. Typhimurium). By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the caecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine caecum. S. Typhimurium used galactarate and glucarate within the gut lumen of streptomycin pre-treated mice, and genetic ablation of the respective catabolic pathways reduced S. Typhimurium competitiveness. Our results identify host-mediated oxidation of carbohydrates in the gut as a mechanism for post-antibiotic pathogen expansion.

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Acknowledgements

This work was supported by Public Health Service grants OD010931 (E.M.V.), AI060555 (S.-P.N.), AI096528 (A.J.B.), AI109799 (R.M.T), AI112241 (C.A.L.), AI112258 (R.M.T), AI112445 (A.J.B.), U24 DK097154 (O.F.), AI112949 (A.J.B.) and AI114922 (A.J.B.).

Author information

Affiliations

  1. Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, California 95616, USA

    • Franziska Faber
    • , Lisa Tran
    • , Mariana X. Byndloss
    • , Christopher A. Lopez
    • , Eric M. Velazquez
    • , Tobias Kerrinnes
    • , Sean-Paul Nuccio
    • , Tamding Wangdi
    • , Renée M. Tsolis
    •  & Andreas J. Bäumler
  2. Genome Center, University of California at Davis, One Shields Avenue, Davis, California 95616, USA

    • Oliver Fiehn
  3. King Abdulaziz University, Biochemistry Department, Jeddah 21412, Saudi Arabia

    • Oliver Fiehn

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Contributions

F.F. performed bacterial growth assays, most animal experiments and analysed the results. O.F. performed GC/MS measurements. M.X.B. scored histological sections. A.J.B., L.T., C.A.L., E.M.V., T.K. and T.W. assisted with animal experiments. F.F., S.-P.N., R.M.T. and A.J.B. were responsible for the overall study design. F.F. and A.J.B. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andreas J. Bäumler.

Reviewer Information Nature thanks D. Bolam, D. Bumann, M. Fischbach & D. M. Monack for their contribution to the peer review of this work.

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https://doi.org/10.1038/nature18597

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