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A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System
Published on: August 30, 2019
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Cecal microbiome transplantation without antibiotic preconditioning standardizes murine microbiomes
Rye Howard-Stone1, Philip Gerwin2, Darien Capunitan2
1School of Computing, University of Connecticut, Storrs, CT, United States.
Frontiers in Microbiology
|August 27, 2025
Summary
Controlled gut microbiome in mice via Cecal Microbiome Transplant (CMT) improves drug development. CMT without antibiotics establishes a stable, wild-type bacterial community, enhancing reproducibility and reducing costs in nonclinical studies.
Area of Science:
- Microbiology
- Pharmacology
- Translational Medicine
Background:
- Uncontrolled gut microbiome variation in mice confounds nonclinical findings, impacting immune maturation, drug metabolism, and translation to clinical settings.
- Microbiome composition is linked to the failure of drug response translation, highlighting the need for standardized animal models.
- Pharmaceutical development faces challenges due to poor reproducibility and high costs associated with variable animal models.
Purpose of the Study:
- To evaluate the stability and effectiveness of establishing a well-characterized, stable bacterial community in laboratory mice using Cecal Microbiome Transplant (CMT).
- To compare CMT with and without antibiotic preconditioning for microbiome modulation.
- To determine the optimal method for creating a reproducible gut microbiome in mice for nonclinical studies.
Main Methods:
- Cecal Microbiome Transplant (CMT) was performed on outbred mouse populations with different initial gut bacterial profiles.
- Methods were compared for establishing a stable bacterial community, with and without prior antibiotic treatment.
- Amplicon Sequence Variant (ASV)-based sequencing was used for high-resolution monitoring of bacterial profiles.
Main Results:
- A single CMT treatment effectively converged mouse populations to a stable, wild-type-like bacterial genetic environment.
- ASV-based monitoring provided higher resolution for tracking bacterial differences compared to species-level analysis.
- Antibiotic preconditioning reduced the efficiency of CMT strain uptake and introduced uncontrolled variance in microbiome composition.
Conclusions:
- CMT without antibiotic preconditioning offers enhanced control over host microbial composition in mice.
- This method improves the utility, accuracy, and relevance of nonclinical drug toxicity and efficacy studies.
- Standardizing the mouse microbiome via CMT can lead to more translatable findings and cost savings in pharmaceutical development.
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