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Updated: Oct 17, 2025
06:51
Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
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In vivo commensal control of Clostridioides difficile virulence
Brintha P Girinathan1, Nicholas DiBenedetto1, Jay N Worley2
1Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell Host & Microbe
|October 12, 2021
Summary
Different gut microbes impact Clostridioides difficile infection severity. Paraclostridium bifermentans protects mice, while Clostridium sardiniense worsens outcomes, highlighting potential therapeutic strategies.
Area of Science:
- Microbiology
- Systems Biology
- Host-Pathogen Interactions
Background:
- Clostridioides difficile infection (CDI) is a major healthcare concern.
- Gut microbiota composition significantly influences CDI outcomes.
- Understanding specific commensal roles is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate how distinct Clostridia species modulate CDI in a mouse model.
- To elucidate the mechanisms by which commensals affect pathogen colonization, growth, and virulence.
- To assess the therapeutic potential of specific commensal species against CDI.
Main Methods:
- Gnotobiotic mouse models colonized with specific Clostridia species.
- In vivo systems biology analyses to study host-commensal-pathogen interactions.
- Assessment of pathogen metabolism, gene regulation, and toxin production.
Main Results:
- Colonization with Paraclostridium bifermentans (amino acid fermenter) reduced CDI severity and improved host survival.
- Colonization with Clostridium sardiniense (butyrate producer) led to more rapid host mortality.
- Commensals altered the gut nutrient environment, impacting C. difficile metabolism and virulence.
- Oral administration of P. bifermentans rescued mice from lethal CDI.
Conclusions:
- Metabolically distinct Clostridia species exert opposing effects on CDI.
- P. bifermentans demonstrates therapeutic potential for CDI treatment.
- Systems biology approaches are valuable for dissecting host-commensal-pathogen dynamics and informing novel therapies.
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