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Development of a Larval Zebrafish Infection Model for Clostridioides difficile
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Modified Mouse Model of Clostridioides difficile Infection as a Platform for Probiotic Efficacy Studies.
T J De Wolfe1,2, A E Kates2,3, L Barko2
1Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA tjdewolfe@gmail.com.
Antimicrobial Agents and Chemotherapy
|April 17, 2019
Summary
Probiotics show promise in reducing Clostridioides difficile infections (CDI). This study found that probiotic treatment delayed CDI onset and relapse in a mouse model, suggesting a potential non-antibiotic approach for CDI management.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Clostridioides difficile infections (CDIs) pose a significant clinical challenge.
- Previous human trials suggest probiotics may reduce CDI duration and alter gut microbiota.
- A need exists for reliable preclinical models to evaluate non-antibiotic CDI interventions.
Purpose of the Study:
- To modify a CDI mouse model to better reflect human clinical outcomes.
- To investigate the efficacy of Lactobacillus and Bifidobacterium probiotics in preventing primary CDI and relapse in this model.
- To identify microbial changes associated with probiotic intervention during CDI.
Main Methods:
- A cefoperazone-induced CDI mouse model was established.
- Mice received either probiotics or placebo during antibiotic treatment and infection challenge.
- Clinical scoring, survival analysis, and 16S rRNA sequencing of stool were performed.
Main Results:
- Probiotic treatment significantly delayed the onset of primary CDI and relapse by 12-24 hours (P < 0.001).
- Mice receiving probiotics showed delayed CDI onset and improved survival.
- Stool microbiome analysis revealed enrichment of Lachnospiraceae in probiotic-treated mice with moderate CDI (P < 0.05).
Conclusions:
- The modified CDI mouse model effectively recapitulates key clinical and microbial features of human CDI.
- Lactobacillus and Bifidobacterium probiotics demonstrate preventative effects against primary CDI and relapse in this model.
- This model provides a valuable platform for further investigation of non-antibiotic strategies for CDI prevention and treatment.
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