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

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 Malik, Alexander Zaborin, Romain Bouziat, Diana R. Ranoa, Mara Wiegerinck, Jordan D. Ernest, Baddr A. Shakhsheer, Irma D. Fleming, Ralph R. Weichselbaum, Dionysios A. Antonopoulos, Jack A. Gilbert, Luis B. Barreiro, Olga Zaborina, Bana Jabri () and John C. Alverdy ()
Additional contact information
Sangman M. Kim: University of Chicago
Jennifer R. DeFazio: University of Chicago
Sanjiv K. Hyoju: University of Chicago
Kishan Sangani: University of Chicago
Robert Keskey: University of Chicago
Monika A. Krezalek: University of Chicago
Nikolai N. Khodarev: University of Chicago
Naseer Sangwan: University of Chicago
Scott Christley: University of Chicago
Katharine G. Harris: University of Chicago
Ankit Malik: University of Chicago
Alexander Zaborin: University of Chicago
Romain Bouziat: 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
Jack A. Gilbert: University of Chicago
Luis B. Barreiro: University of Chicago
Olga Zaborina: University of Chicago
Bana Jabri: University of Chicago
John C. Alverdy: University of Chicago

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15545-w

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DOI: 10.1038/s41467-020-15545-w

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