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Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity

Author

Listed:
  • Sangman M. Kim

    (University of Chicago
    University of Chicago
    University of San Francisco)

  • Jennifer R. DeFazio

    (University of Chicago
    Columbia University)

  • Sanjiv K. Hyoju

    (University of Chicago)

  • Kishan Sangani

    (University of Chicago
    University of Chicago)

  • Robert Keskey

    (University of Chicago
    University of Chicago)

  • Monika A. Krezalek

    (University of Chicago)

  • Nikolai N. Khodarev

    (University of Chicago)

  • Naseer Sangwan

    (University of Chicago
    Argonne National Laboratory)

  • Scott Christley

    (University of Chicago)

  • Katharine G. Harris

    (University of Chicago)

  • Ankit Malik

    (University of Chicago
    University of Chicago)

  • Alexander Zaborin

    (University of Chicago)

  • Romain Bouziat

    (University of Chicago
    University of Chicago)

  • Diana R. Ranoa

    (University of Chicago)

  • Mara Wiegerinck

    (University of Chicago)

  • Jordan D. Ernest

    (University of Chicago)

  • Baddr A. Shakhsheer

    (University of Chicago)

  • Irma D. Fleming

    (University of Chicago)

  • Ralph R. Weichselbaum

    (University of Chicago)

  • Dionysios A. Antonopoulos

    (University of Chicago
    Argonne National Laboratory)

  • Jack A. Gilbert

    (University of Chicago
    Argonne National Laboratory)

  • Luis B. Barreiro

    (University of Chicago
    University of Montreal
    University of Montreal)

  • Olga Zaborina

    (University of Chicago)

  • Bana Jabri

    (University of Chicago
    University of Chicago
    University of Chicago
    University of Chicago)

  • John C. Alverdy

    (University of Chicago)

Abstract

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.

Suggested Citation

  • Sangman M. Kim & Jennifer R. DeFazio & Sanjiv K. Hyoju & Kishan Sangani & Robert Keskey & Monika A. Krezalek & Nikolai N. Khodarev & Naseer Sangwan & Scott Christley & Katharine G. Harris & Ankit Mali, 2020. "Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15545-w
    DOI: 10.1038/s41467-020-15545-w
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