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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Bacillus subtilis spores reduce susceptibility to Citrobacter rodentium-mediated enteropathy in a mouse model
Rossana D'Arienzo1, Francesco Maurano, Giuseppe Mazzarella
1Istituto di Scienze dell'Alimentazione, CNR, via Roma 52, 83100 Avellino, Italy.
Abstract:
The present work was aimed at investigating whether Bacillus subtilis spores, widely used in probiotic as well as pharmaceutical preparations for mild gastrointestinal disorders, can suppress enteric infections. To address this issue, we developed a mouse model of infection using the mouse enteropathogen Citrobacter rodentium, a member of a family of human and animal pathogens which includes the clinically significant enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli strains. This group of pathogens causes transmissible colonic hyperplasia by using attaching and effacing (A/E) lesions to colonize the host colon. Because of its similarities to human enteropathogens, C. rodentium is now widely used as an in vivo model for gastrointestinal infections. Swiss NIH mice were orally administered B. subtilis spores one day before infection with C. rodentium. Mice were sacrificed on day 15 after infection, and distal colon, liver and mesenteric lymph nodes were removed for bacteria counts, morphology, immunohistology and IFNgamma mRNA analysis. We observed that spore predosing was effective in significantly decreasing infection and enteropathy in suckling mice infected with a dose of C. rodentium sufficient to cause colon colonization, crypt hyperplasia and high mortality rates. Moreover, in mice predosed with spores, the number of CD4(+) cells and IFNgamma transcript levels remained high. These results thus indicate that our newly established model of C. rodentium infection is a suitable system for analyzing the effects of probiotic bacteria on enteroinfections and that B. subtilis spores are efficient at reducing C. rodentium infection in mice, leaving unaltered the immune response against the pathogen.
Insights
Bacillus subtilis spores effectively reduced Citrobacter rodentium infection in mice. This probiotic approach suppressed enteric infections and enteropathy without altering the host immune response against the pathogen.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Bacillus subtilis spores are utilized in probiotics and pharmaceuticals for gastrointestinal issues.
- Enteric infections caused by pathogens like Citrobacter rodentium pose significant health risks.
- Citrobacter rodentium serves as a relevant model for studying human enteropathogens such as enteropathogenic (EPEC) and enterohemorrhagic (EHEC) E. coli.
Purpose of the Study:
- To investigate the efficacy of Bacillus subtilis spores in suppressing enteric infections.
- To establish and utilize a mouse model for analyzing probiotic effects on enteroinfections.
Main Methods:
- A mouse model was developed using Citrobacter rodentium infection.
- Swiss NIH mice were orally administered Bacillus subtilis spores prior to C. rodentium infection.
- Infection levels, enteropathy, and immune responses (IFN-gamma mRNA, CD4+ cells) were assessed in collected tissues.
Main Results:
- Bacillus subtilis spore predosing significantly reduced C. rodentium infection and associated enteropathy in mice.
- Spore treatment decreased colon colonization, crypt hyperplasia, and mortality rates.
- Immune markers, including CD4+ cell counts and IFN-gamma transcript levels, remained elevated in spore-treated mice.
Conclusions:
- Bacillus subtilis spores demonstrate significant potential in mitigating enteric infections caused by C. rodentium.
- The established mouse model is suitable for evaluating probiotic interventions against enteroinfections.
- Probiotic administration of B. subtilis spores effectively combats C. rodentium infection while preserving a robust immune response.

