C. Rodentium-Induced Colitis

Description

Citrobacter rodentium is a murine, gram-negative, facultative anaerobic enteropathogen with genetic properties and virulence factors that evoke an inflammatory response similar to that induced in humans by enteropathogenic Escherichia coli (EPEC). Infectious colitis induced with C. rodentium is therefore a clinically relevant, translational model of intestinal dysbiosis with a range of phenotypic severity based on the host mouse strain. This model can be utilized to assess the efficacy of novel therapeutics against EPEC or to characterize the behavior of test compounds in a pathogen-induced, inflammatory setting. C. rodentium infection in C57Bl/6 mice via oral gavage induces self-limiting disease that is typically characterized by weight loss, increased rates of diarrhea/blood in the stool, and colonic inflammation. The representative data depicts a model of C. rodentium infectious colitis with a microbiome targeted treatment paradigm of fecal microbiota transfers from animals with segmented filamentous bacteria (SFB) into confirmed SFB- animals.

  • Advantages: translational animal model for EPEC, established intestinal epithelial barrier disruption.
  • Disadvantages: non-human pathogen, high inoculating doses required in C57Bl/6 mice for disease induction.
Model Systems
  • C57Bl/6 Mice
Standard Readouts
  • Percent weight change
  • Disease Activity Index: diarrhea and blood in stool scoring
  • Terminal colon weight and length measurement
Additional Readouts
  • Survival
  • Endoscopy
  • Intestinal and systemic bacterial burden
  • Terminal histopathology and/or IHC analyses
  • Colon cytokines
  • Peripheral lymphoid organ immunophenotyping
  • Intestinal lamina propria immunophenotyping
  • Custom assays
Representative DataClick Image to Enlarge
Percent Weight Change in a Murine Model of C. rodentium-Induced Infectious Colitis

Animals are weighed daily, and percent body weight change relative to Day 0 is calculated. AUCs are calculated to compare groups and are shown in the figure inset (*p<0.05; ****p<0.0001).

Diarrhea Incidence in a Murine Model of C. rodentium-Induced Infectious Colitis

Animals are observed for diarrhea on a daily basis and the overall incidence rates are calculated and compared to Group 4 (*p<0.05; **p<0.01).

Colon Weight:Length Ratio in a Murine Model of C. rodentium-Induced Infectious Colitis

Colons are excised, measured, and weighed on Day 14. Colon weight:length ratios are calculated and compared to Group 4 (****p<0.0001).

Fecal Bacterial Burden Kinetics in a Murine Model of C. rodentium-Induced Infectious Colitis

Feces are collected throughout the study from Groups 2-5, homogenized, and plated for C. rodentium CFU enumeration. All groups are compared to Group 4 (*p<0.05; **p<0.01).

Bacterial Burden of Critical Organs in a Murine Model of C. rodentium-Induced Infectious Colitis

Day 14 livers and cecums/colons are collected from all groups, homogenized, and plated for C. rodentium CFU enumeration. CFU/mL (left) and CFU/g (right) are shown.

Daniel Lichtman

Managing Partner