Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.
Animals
Butyric Acid
/ metabolism
Fecal Microbiota Transplantation
Feces
/ chemistry
Gastrointestinal Microbiome
Gastrointestinal Tract
/ pathology
Histone Deacetylase Inhibitors
/ pharmacology
Humans
Immunity
Interferon Regulatory Factor-3
/ metabolism
Male
Mice, Inbred C57BL
Sepsis
/ immunology
Signal Transduction
Transcription, Genetic
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 05 2020
11 05 2020
Historique:
received:
20
08
2019
accepted:
11
03
2020
entrez:
13
5
2020
pubmed:
13
5
2020
medline:
6
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32393794
doi: 10.1038/s41467-020-15545-w
pii: 10.1038/s41467-020-15545-w
pmc: PMC7214422
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Interferon Regulatory Factor-3
0
Irf3 protein, mouse
0
Butyric Acid
107-92-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2354Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK042086
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM062344
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007074
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007281
Pays : United States
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