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Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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The Gut Microbiome and Butyrate Differentiate Clostridioides difficile Colonization and Infection in Children
Maribeth R Nicholson1, Siyuan Ma2, Britton A Strickland2
1Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
The Journal of Infectious Diseases
|December 11, 2025
Summary
The gut microbiome and butyrate levels differ between children with asymptomatic Clostridioides difficile colonization and symptomatic infection. These differences may play a role in developing Clostridioides difficile infection symptoms.
Area of Science:
- Microbiology
- Gastroenterology
- Pediatrics
Background:
- Clostridioides difficile infection (CDI) causes significant illness, but asymptomatic colonization also occurs.
- Toxins alone do not distinguish between CDI and asymptomatic colonization in children.
- Other factors, like the gut microbiome and metabolites, may influence CDI development.
Purpose of the Study:
- To investigate differences in the intestinal microbiome and butyrate levels between children with CDI and asymptomatic colonization.
- To identify microbial and metabolic factors associated with symptomatic CDI versus colonization.
Main Methods:
- A case-control study compared 55 children with symptomatic CDI to 50 asymptomatic children colonized with C. difficile.
- Stool samples were analyzed using 16S rRNA sequencing for microbiome composition.
- Butyrate levels were quantified using liquid chromatography-mass spectrometry.
Main Results:
- Symptomatic CDI was strongly associated with altered gut microbial abundance, including increased Escherichia/Shigella and Haemophilus, and decreased Faecalibacterium and Bifidobacterium.
- A depletion in microbial butyrate producers and fecal butyrate was observed in children with symptomatic CDI compared to those with asymptomatic colonization.
- Gut microbiota composition differences were more significant than clinical factors in distinguishing CDI status.
Conclusions:
- Significant differences exist in the gut microbiota and butyrate levels between asymptomatic C. difficile colonization and symptomatic CDI in children.
- These microbial and metabolic alterations suggest a potential role in the pathogenesis of symptomatic CDI.
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