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Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

Author

Listed:
  • Casey M. Theriot

    (The University of Michigan
    The University of Michigan)

  • Mark J. Koenigsknecht

    (The University of Michigan
    The University of Michigan)

  • Paul E. Carlson

    (The University of Michigan)

  • Gabrielle E. Hatton

    (The University of Michigan)

  • Adam M. Nelson

    (The University of Michigan
    The University of Michigan)

  • Bo Li

    (The University of Michigan)

  • Gary B. Huffnagle

    (The University of Michigan)

  • Jun Z. Li

    (The University of Michigan)

  • Vincent B. Young

    (The University of Michigan
    The University of Michigan)

Abstract

Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.

Suggested Citation

  • Casey M. Theriot & Mark J. Koenigsknecht & Paul E. Carlson & Gabrielle E. Hatton & Adam M. Nelson & Bo Li & Gary B. Huffnagle & Jun Z. Li & Vincent B. Young, 2014. "Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4114
    DOI: 10.1038/ncomms4114
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    Cited by:

    1. Rui Xu & Wandy L. Beatty & Valentin Greigert & William H. Witola & L. David Sibley, 2024. "Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Emily C Woods & Adrianne N Edwards & Kevin O Childress & Joshua B Jones & Shonna M McBride, 2018. "The C. difficile clnRAB operon initiates adaptations to the host environment in response to LL-37," PLOS Pathogens, Public Library of Science, vol. 14(8), pages 1-28, August.
    3. Alexander Y. G. Yip & Olivia G. King & Oleksii Omelchenko & Sanjana Kurkimat & Victoria Horrocks & Phoebe Mostyn & Nathan Danckert & Rohma Ghani & Giovanni Satta & Elita Jauneikaite & Frances J. Davie, 2023. "Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Jordy Evan Sulaiman & Jaron Thompson & Yili Qian & Eugenio I. Vivas & Christian Diener & Sean M. Gibbons & Nasia Safdar & Ophelia S. Venturelli, 2024. "Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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