Related Experiment Video
Updated: Jun 6, 2025
Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
Microbiome impact of ibezapolstat and other Clostridioides difficile infection relevant antibiotics using humanized
Background:
Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics.
Methods:
Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare gut microbiome perturbation between treatment and no-drug control groups.
Results:
Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversity following FDX- and IBZ-treated groups were less pronounced compared to those observed in VAN-or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum).
Conclusion:
In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity compared to VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.
Insights
Ibezapolstat (IBZ) and fidaxomicin (FDX) showed minimal gut microbiome disruption compared to vancomycin (VAN) and metronidazole (MET) in mice. IBZ and FDX offer potentially favorable microbiome profiles for treating Clostridioides difficile infection (CDI).
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Ibezapolstat (IBZ) is an investigational drug targeting bacterial Pol IIIC for Clostridioides difficile infection (CDI).
- Prior research indicated IBZ preserves microbiome diversity better than vancomycin (VAN).
- Head-to-head comparisons with other CDI antibiotics were lacking.
Purpose of the Study:
- To compare the impact of IBZ on gut microbiome diversity against other standard-of-care CDI antibiotics.
- To evaluate alterations in microbial composition and diversity profiles induced by different CDI treatments.
Main Methods:
- Germ-free mice received human fecal microbiota transplants.
- Mice were treated with IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control).
- 16S rRNA gene sequencing analyzed temporal changes in stool microbial communities.
Main Results:
- Metronidazole (MET) caused the most significant microbiome diversity reduction.
- FDX and IBZ treatments resulted in less pronounced changes in alpha and beta diversity compared to VAN and MET.
- IBZ and FDX increased Bacteroidota abundance; IBZ also increased Actinomycetota.
Conclusions:
- IBZ and FDX demonstrate a more favorable gut microbiome profile compared to VAN and MET in a mouse model.
- Distinct microbiome alterations were observed between IBZ and FDX, suggesting potential for differentiation.
- These findings support IBZ as a potentially microbiome-sparing option for CDI treatment.
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