Related Experiment Video
Updated: Dec 21, 2025
Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
Sangman M Kim1,2,3, Jennifer R DeFazio4,5, Sanjiv K Hyoju4
1Committee on Immunology, University of Chicago, Chicago, IL, USA.
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.
Insights
Fecal microbiota transplants (FMT) can reverse lethal sepsis in mice by restoring host immunity and enhancing pathogen clearance. This treatment boosts butyrate-producing bacteria, suggesting FMT as a potential sepsis therapy.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Sepsis is a life-threatening condition in intensive care units, often caused by multi-drug-resistant pathogens.
- Sepsis is associated with suppressed host immunity and reduced expression of key immune-related genes and metabolites like butyrate.
- Specific pathogen communities can cause lethal sepsis by suppressing host defense mechanisms.
Purpose of the Study:
- To investigate the impact of a defined pathogen community on host gene expression and butyrate levels during sepsis.
- To evaluate the efficacy of fecal microbiota transplantation (FMT) in reversing sepsis-induced immunosuppression and lethality.
- To elucidate the role of interferon regulatory factor 3 (IRF3) and butyrate-producing bacteria in FMT's protective effects.
Main Methods:
- Induction of sepsis in mice using a defined four-member pathogen community.
- Analysis of host transcriptome to identify suppressed immune pathways.
- Measurement of butyrate levels in the gut.
- Administration of fecal microbiota transplant (FMT) to septic mice.
- Assessment of pathogen clearance, host immune restoration, and survival rates.
- Evaluation of IRF3-dependent mechanisms and Bacteroidetes expansion post-FMT.
Main Results:
- Sepsis induced by the pathogen community led to systemic suppression of host genes crucial for pathogen clearance and decreased butyrate expression.
- Pathogens directly suppressed interferon regulatory factor 3 (IRF3).
- FMT reversed lethal sepsis, significantly enhancing pathogen clearance through IRF3-dependent restoration of host immunity.
- The protective effect of FMT was associated with the expansion of butyrate-producing Bacteroidetes.
Conclusions:
- Sepsis involves pathogen-induced suppression of critical host immune pathways, including IRF3 signaling.
- Fecal microbiota transplantation (FMT) effectively restores host immunity and enhances pathogen clearance in a sepsis model.
- FMT's therapeutic benefits in sepsis are linked to IRF3 activation and the expansion of beneficial butyrate-producing bacteria, suggesting its potential as a novel treatment strategy.
