Gnotobiotic OMM12 mice support sustained Clostridioides difficile colonization without antibiotic pretreatment
- 1Institut Pasteur, Paris (France)
Abstract
Antibiotic-induced disruption of the intestinal microbiota predispose individuals to Clostridioides difficile infection (CDI). Although several animal models reproduce acute CDI, sustained colonization in the presence of a defined resident microbiota remains challenging to study. Here, we show that gnotobiotic OMM12 mice support sustained colonization for at least 20 days following oral challenge with either the reference CD630{Delta}erm strain or the clinical R20291 (RT027) strain, without prior antibiotic treatment. Early infection induced transient weight loss, rapid intestinal inflammation and transient shifts in the relative abundance of resident bacterial species. By day 20, inflammatory markers had largely resolved, and the resident microbiota had shifted back towards its baseline composition, despite continued detection of C. difficile vegetative cells, spores and toxins. Early bacterial community perturbations were not accompanied by detectable changes in the resident prophage induction. Moreover, whole-genome sequencing of C. difficile clones recovered at day 20 showed no detectable gut-specific genomic adaptation relative to the inoculum. Similar colonization kinetics and clinical outcomes were observed across independent experiments conducted over five years, supporting the consistent reproducibility of this model. Together, OMM12 mice provide a defined, antibiotic-free and experimentally tractable framework to investigate host-microbiota-pathogen interactions during sustained C. difficile colonization and a robust platform for therapeutic development.
Related
- Mechanistic prediction of fecal microbiota transplant engraftment and Clostridioides difficile colonization resistance with μODE
- Successful coral microbiome transplant from high to low heat tolerant corals requires antibiotic pretreatment
- A Gnotobiotic Rice Pathosystem Reveals How the Microbiome Suppresses Rice Blast Disease
- In silico assessment of barnyard millet and blue pea derived bioactive peptides against Salmonella enterica Serovar Typhi and Clostridioides difficile
- Metabolic network restoration, not donor microbial engraftment, associates with resolution of recurrent Clostridioides difficile infection
BibTeX
@misc{conti2026gnotobiotic,
title = {{Gnotobiotic OMM12 mice support sustained Clostridioides difficile colonization without antibiotic pretreatment}},
author = {D. E. Conti and E. Chatonnat and Q. Lamy-Besnier and T. Manivannan and A. Crouzols and L. C. Caulat and C. Mulet and M. Berard and L. Debarbieux and B. Dupuy and J. R. Garneau},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762127},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762127v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Gnotobiotic OMM12 mice support sustained Clostridioides difficile colonization without antibiotic pretreatment
AU - D. E. Conti
AU - E. Chatonnat
AU - Q. Lamy-Besnier
AU - T. Manivannan
AU - A. Crouzols
AU - L. C. Caulat
AU - C. Mulet
AU - M. Berard
AU - L. Debarbieux
AU - B. Dupuy
AU - J. R. Garneau
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762127
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762127v1
AB - Antibiotic-induced disruption of the intestinal microbiota predispose individuals to Clostridioides difficile infection (CDI). Although several animal models reproduce acute CDI, sustained colonization in the presence of a defined resident microbiota remains challenging to study. Here, we show that gnotobiotic OMM12 mice support sustained colonization for at least 20 days following oral challenge with either the reference CD630{Delta}erm strain or the clinical R20291 (RT027) strain, without prior antibiotic treatment. Early infection induced transient weight loss, rapid intestinal inflammation and transient shifts in the relative abundance of resident bacterial species. By day 20, inflammatory markers had largely resolved, and the resident microbiota had shifted back towards its baseline composition, despite continued detection of C. difficile vegetative cells, spores and toxins. Early bacterial community perturbations were not accompanied by detectable changes in the resident prophage induction. Moreover, whole-genome sequencing of C. difficile clones recovered at day 20 showed no detectable gut-specific genomic adaptation relative to the inoculum. Similar colonization kinetics and clinical outcomes were observed across independent experiments conducted over five years, supporting the consistent reproducibility of this model. Together, OMM12 mice provide a defined, antibiotic-free and experimentally tractable framework to investigate host-microbiota-pathogen interactions during sustained C. difficile colonization and a robust platform for therapeutic development.
ER -