A Mouse Model of Clostridium difficile Infection (CDI) Suitable for Study of Human Fecal Microbiota Transplantation (FMT)

Introduction: The treatment of choice for multiply-recurrent CDI in humans is fecal microbiota transplantation (FMT), with an efficacy rate as high as 90 percent. However, there are still many unanswered questions despite efficacy of FMT, such as what are the active components, how long will FMT last, and what are the kinetics of microbiota change before, during and after FMT. These questions may best be answered in an accurate and reliable animal model. Methods: We developed a mouse model of CDI in which 7 fasting mice were challenged intragastrically with 105 viable C. difficile, strain ATCC 43255. The definition of diarrhea was determined according to the modified human Bristol Stool Chart. All 7 mice developed CDI and treated on day 1 with FMT product (200μL). FMT products were obtained from healthy human donor via gavage. Results: Fifty-five stool samples were collected from the mice during 6 weeks of study. DNA was extracted from all samples for quantitative PCR (qPCR) analysis. All mice developed CDI after challenge with C. difficile strain(s). qPCR analysis detected the concentration of Clostridium, Bacteroides, Biffidobacterium, Lactorbacillus species and Escherichia coli in all fecal DNA samples. A significant 1.5 fold increase in the concentration of Clostridium increased in fecal samples collected before antibiotics treatment and after antibiotics treatment (PBifidobacterium was significant reduced (1.9 fold) in fecal samples from mice with CDI undergoing FMT (p=0.0011). One day after FMT, Bacteroides increased 1.2 fold (P=0.6316). For 2/7 animal surviving until 8 days after the FMT, Clostridium spp. decreased 1.27 fold (PBacteroides increased 1.3 fold (P=0.0079). Conclusion: In conclusion, we developed an animal model that responds to human FMT product and showed quantitative changes in microbiota after FMT resembling the changes seen in humans.