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Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism

Author

Listed:
  • Amir Zarrinpar

    (The Salk Institute
    University of California, San Diego
    University of California, San Diego
    VA San Diego Health Systems)

  • Amandine Chaix

    (The Salk Institute)

  • Zhenjiang Z. Xu

    (University of California, San Diego
    University of California, San Diego
    University of California, San Diego)

  • Max W. Chang

    (The Salk Institute
    University of California, San Diego)

  • Clarisse A. Marotz

    (University of California, San Diego
    University of California, San Diego)

  • Alan Saghatelian

    (The Salk Institute)

  • Rob Knight

    (University of California, San Diego
    University of California, San Diego
    University of California, San Diego)

  • Satchidananda Panda

    (The Salk Institute)

Abstract

Antibiotic-induced microbiome depletion (AIMD) has been used frequently to study the role of the gut microbiome in pathological conditions. However, unlike germ-free mice, the effects of AIMD on host metabolism remain incompletely understood. Here we show the effects of AIMD to elucidate its effects on gut homeostasis, luminal signaling, and metabolism. We demonstrate that AIMD, which decreases luminal Firmicutes and Bacteroidetes species, decreases baseline serum glucose levels, reduces glucose surge in a tolerance test, and improves insulin sensitivity without altering adiposity. These changes occur in the setting of decreased luminal short-chain fatty acids (SCFAs), especially butyrate, and the secondary bile acid pool, which affects whole-body bile acid metabolism. In mice, AIMD alters cecal gene expression and gut glucagon-like peptide 1 signaling. Extensive tissue remodeling and decreased availability of SCFAs shift colonocyte metabolism toward glucose utilization. We suggest that AIMD alters glucose homeostasis by potentially shifting colonocyte energy utilization from SCFAs to glucose.

Suggested Citation

  • Amir Zarrinpar & Amandine Chaix & Zhenjiang Z. Xu & Max W. Chang & Clarisse A. Marotz & Alan Saghatelian & Rob Knight & Satchidananda Panda, 2018. "Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05336-9
    DOI: 10.1038/s41467-018-05336-9
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    Cited by:

    1. Lukas Hafner & Maxime Pichon & Christophe Burucoa & Sophie H. A. Nusser & Alexandra Moura & Marc Garcia-Garcera & Marc Lecuit, 2021. "Listeria monocytogenes faecal carriage is common and depends on the gut microbiota," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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