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; John C. Alverdy

doi:10.1038/s41467-020-15545-w

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. AntonopoulosJack A. Gilbert, Luis B. Barreiro, Olga Zaborina, Bana Jabri, John C. Alverdy

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	2354
Journal	Nature communications
Volume	11
Issue number	1
Early online date	May 11 2020
DOIs	https://doi.org/10.1038/s41467-020-15545-w
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Online availability

10.1038/s41467-020-15545-wLicense: CC BY

Library availability

Discover UIUC Full Text

Cite this

Kim, S. M., DeFazio, J. R., Hyoju, S. K., Sangani, K., Keskey, R., Krezalek, M. A., Khodarev, N. N., Sangwan, N., Christley, S., Harris, K. G., Malik, A., Zaborin, A., Bouziat, R., Ranoa, D. R., Wiegerinck, M., Ernest, J. D., Shakhsheer, B. A., Fleming, I. D., Weichselbaum, R. R., ... Alverdy, J. C. (2020). Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity. Nature communications, 11(1), Article 2354. https://doi.org/10.1038/s41467-020-15545-w

Kim, SM, DeFazio, JR, Hyoju, SK, Sangani, K, Keskey, R, Krezalek, MA, Khodarev, NN, Sangwan, N, Christley, S, Harris, KG, Malik, A, Zaborin, A, Bouziat, R, Ranoa, DR, Wiegerinck, M, Ernest, JD, Shakhsheer, BA, Fleming, ID, Weichselbaum, RR, Antonopoulos, DA, Gilbert, JA, Barreiro, LB, Zaborina, O, Jabri, B & Alverdy, JC 2020, 'Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity', Nature communications, vol. 11, no. 1, 2354. https://doi.org/10.1038/s41467-020-15545-w

@article{c157fe2effe14535af30321ac51710f7,

title = "Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-15545-w",

language = "English (US)",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity

AU - Kim, Sangman M.

AU - DeFazio, Jennifer R.

AU - Hyoju, Sanjiv K.

AU - Sangani, Kishan

AU - Keskey, Robert

AU - Krezalek, Monika A.

AU - Khodarev, Nikolai N.

AU - Sangwan, Naseer

AU - Christley, Scott

AU - Harris, Katharine G.

AU - Malik, Ankit

AU - Zaborin, Alexander

AU - Bouziat, Romain

AU - Ranoa, Diana R.

AU - Wiegerinck, Mara

AU - Ernest, Jordan D.

AU - Shakhsheer, Baddr A.

AU - Fleming, Irma D.

AU - Weichselbaum, Ralph R.

AU - Antonopoulos, Dionysios A.

AU - Gilbert, Jack A.

AU - Barreiro, Luis B.

AU - Zaborina, Olga

AU - Jabri, Bana

AU - Alverdy, John C.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85084474983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85084474983&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-15545-w

DO - 10.1038/s41467-020-15545-w

M3 - Article

C2 - 32393794

AN - SCOPUS:85084474983

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2354

ER -

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

Abstract

ASJC Scopus subject areas

Online availability

Library availability

Related links

Fingerprint

Cite this