The Microbiota Dictates Vendor-Derived Differences in a Murine Clostridioides difficile Infection Model
- 1McGill University
Abstract
Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea and remains a major burden to healthcare systems worldwide. The development of novel therapeutics for CDI requires robust and reproducible preclinical models. However, the microbiota has emerged as a major source of variability in animal studies. Here, we found that genetically similar mice obtained from two commercial vendors, Jackson Laboratory (JAX) and Charles River Laboratories (CRL), exhibited marked differences in susceptibility to CDI, with JAX mice developing fulminant disease and CRL mice remaining resistant. Using full-length 16S rRNA gene sequencing, we show that JAX and CRL mice harboured distinct gut microbiota, and that cohousing susceptible JAX mice with resistant CRL mice was sufficient to shift the JAX microbiota toward the CRL community structure and confer resistance to CDI. Differential abundance analysis identified taxa distinguishing resistant and susceptible mice, providing candidates for future mechanistic investigation. These findings demonstrate that vendor-derived variation in the gut microbiota drives differential susceptibility to CDI in mice, and that this phenotype is transferable via cohousing, highlighting the importance of accounting for the microbiota when designing and interpreting animal models of infectious disease.
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BibTeX
@misc{keogh2026microbiota,
title = {{The Microbiota Dictates Vendor-Derived Differences in a Murine Clostridioides difficile Infection Model}},
author = {L. Keogh and L. Dridi and B. Thurairajah and M. Shamash and C. F. Maurice and I. L. King and B. Castagner},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748273},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748273v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - The Microbiota Dictates Vendor-Derived Differences in a Murine Clostridioides difficile Infection Model
AU - L. Keogh
AU - L. Dridi
AU - B. Thurairajah
AU - M. Shamash
AU - C. F. Maurice
AU - I. L. King
AU - B. Castagner
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748273
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748273v1
AB - Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea and remains a major burden to healthcare systems worldwide. The development of novel therapeutics for CDI requires robust and reproducible preclinical models. However, the microbiota has emerged as a major source of variability in animal studies. Here, we found that genetically similar mice obtained from two commercial vendors, Jackson Laboratory (JAX) and Charles River Laboratories (CRL), exhibited marked differences in susceptibility to CDI, with JAX mice developing fulminant disease and CRL mice remaining resistant. Using full-length 16S rRNA gene sequencing, we show that JAX and CRL mice harboured distinct gut microbiota, and that cohousing susceptible JAX mice with resistant CRL mice was sufficient to shift the JAX microbiota toward the CRL community structure and confer resistance to CDI. Differential abundance analysis identified taxa distinguishing resistant and susceptible mice, providing candidates for future mechanistic investigation. These findings demonstrate that vendor-derived variation in the gut microbiota drives differential susceptibility to CDI in mice, and that this phenotype is transferable via cohousing, highlighting the importance of accounting for the microbiota when designing and interpreting animal models of infectious disease.
ER -