Modified Mouse Model of Clostridioides difficile Infection as a Platform for Probiotic Efficacy Studies

• Published in: Antimicrobial agents and chemotherapy Vol. 63; no. 7
• Main Authors: De Wolfe, T J, Kates, A E, Barko, L, Darien, B J, Safdar, N
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-07-2019
• Subjects: Animals; Bifidobacterium - genetics; Bifidobacterium - physiology; Clinical Therapeutics; Clostridium difficile; Clostridium difficile - genetics; Clostridium difficile - pathogenicity; Clostridium Infections; Clostridium Infections - microbiology; Clostridium Infections - prevention & control; Gastrointestinal Microbiome - physiology; Lactobacillus; Lactobacillus - genetics; Lactobacillus - physiology; Male; Mice; Mice, Inbred C57BL; Preventive Medicine; Preventive Medicine - methods; Probiotics; Probiotics - therapeutic use; RNA, Ribosomal, 16S - genetics; gastrointestinal; CDI; preventative medicine; antibiotics; microbiome; Lactobacillus
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.00111-19

Probiotics may represent a promising approach for reducing
(
)
infections (CDIs). A clinical trial conducted by our group demonstrated that CDI patients undergoing adjunctive treatment with
and
probiotics had a reduction in diarrheal duration and compositional changes in their stool microbiomes. Here, we modified a CDI mouse model to represent clinical outcomes observed in patients and employed this model to identify evidence for the prevention of primary CDI and relapse with the same probiotic. Mice (
 = 80) were administered 0.25 mg/ml cefoperazone over 5 days and subsequently challenged with 10
VPI 10463 spores. A subset of mice (
 = 40) were administered 10
CFU of probiotics daily alongside cefoperazone pretreatment and until experimental endpoints were reached. Clinical scoring was performed daily on mice and used to evaluate CDI onset and severity. Moderate CDI in mice was defined by survival beyond day 3 postinfection, while mice with severe CDI were those who succumbed to infection prior to day 3 postinfection. Sequencing and analysis of 16S rRNA from stool content were performed to determine compositional alterations to the microbiota. Using total clinical scores, we identified an association between probiotic treatment and delayed onset of primary CDI and relapse by approximately 12 to 24 h (
0.001). The stool microbiome of mice with moderate CDI receiving probiotic treatment was significantly enriched with
during primary CDI (
0.05). The outcomes observed present an opportunity to use this modified CDI mouse model to examine the efficacy of nonantibiotic options for CDI management.