Development of a Standardized Scoring System to Assess a Murine Model of <i>Clostridium difficile</i> Colitis

Shelby, Rita D.; Tengberg, Natalie; Conces, Miriam; Olson, Jacob K.; Navarro, Jason B.; Bailey, Michael T.; Goodman, Steven D.; Besner, Gail E.

doi:10.1080/08941939.2019.1571129

Cited by 18 publications

(26 citation statements)

References 22 publications

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“…Antibiotics were administered over the course of 4 d in the form of a water cocktail as we have previously described. 12 The water cocktail contained kanamycin (0.4 mg/mL), gentamicin (0.035 mg/mL), colistin (850 U/mL), metronidazole (0.215 mg/mL), and vancomycin (0.045 mg/mL), in the manner described by Julia et al 16 and by Chen et al 17 Antibiotics were purchased from Sigma-Aldrich (St. Louis, MO), reconstituted in sterile water, and provided to the mice ad libitum in their drinking water. The antibiotic concentrations were calculated based on an average weight of the mice used (20-25 gm), and expected water consumption over 4 d (4-6 mL/mouse/day).…”

Section: Antibiotic Administrationmentioning

confidence: 99%

“…A CSS of 6 or greater is considered consistent with C. difficile colitis, as we have previously reported. 12 Animals achieving a CSS of ≥6 were euthanized. Upon sacrifice, the entire colon and cecum were collected for analysis.…”

Section: Changes In Weight Clinical Sickness Scoring and Histopatholmentioning

confidence: 99%

“…Our previous work supported this notion by establishing novel clinical and histological scoring systems that allow for efficient and accurate identification of diseased animals in an experimental murine model of C. difficile colitis. 12 We now incorporate these scoring systems to validate disease inoculation and to analyze the use of probiotics to prevent and treat C. difficile infection.…”

Section: Introductionmentioning

confidence: 99%

“…Combined final scores for each mouse range from 0 to 12, with the total score recorded in the final analysis. A CSS of 6 or greater is considered consistent with C. difficile colitis 12.…”

mentioning

confidence: 99%

“…Scores in these categories range from no injury (0) to severe injury (3), and are combined into a cumulative HIS score ranging from 0 to 9. A HIS of ≥4 is indicative of C. difficile colitis 12. LU, lumen; LP, lamina propria, S, submucosa, thick arrow, level of mucosal injury; thin arrow, superficial epithelium injury.…”

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confidence: 99%

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A novel probiotic therapeutic in a murine model of Clostridioides difficile colitis

et al. 2020

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Clostridioides difficile infection (CDI) is a common cause of antimicrobial-associated diarrhea. Probiotics have shown variable results in decreasing its incidence and severity. We examined the efficacy of Lactobacillus reuteri administered using a novel probiotic biofilm delivery system in the treatment and prevention of CDI in a murine model.For prophylactic therapy, mice received an oral antibiotic cocktail followed by clindamycin injection, followed by probiotic administration (planktonic vs. biofilm state), followed by C. difficile oral gavage. For treatment therapy, mice received antibiotics and C. difficile first, followed by probiotic administration. Clinical sickness scores (CSS) and intestinal histologic injury scores (HIS) were assigned.In the Prophylactic Therapy model, CSS: 67% of untreated mice exposed to C. difficile demonstrated CSS ≥ 6, which is consistent with C. difficile infection (p< .001 compared to unexposed mice). In mice treated with planktonic Lr, 55% had a CSS ≥ 6, but only 19% of mice treated with Lr in its biofilm state had CSS ≥ 6 (p< .001). Mice receiving Lr + DM-Maltose lost the least amount of weight compared to mice receiving saline (p = .004676) or to mice receiving Lr (p= .003185). HIS: 77% of untreated mice exposed to C. difficile had HIS scores ≥4, which is consistent with C. difficile infection. In mice treated with planktonic Lr, 62% had HIS ≥4, but only 19% of mice treated with Lr in its biofilm state had HIS ≥4. (p< .001). Additionally, mice treated with Lr in its biofilm state had better survival compared to untreated mice and to mice treated with planktonic Lr (p ≤ 0.05). Similar findings for weight loss, CSS, HIS and survival were obtained for Treatment Therapy.A single dose of Lactobacillus reuteri in its biofilm state reduces the severity and incidence of experimental C. difficile infection when administered as both prophylactic and treatment therapy.

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Section: Antibiotic Administrationmentioning

confidence: 99%

Section: Changes In Weight Clinical Sickness Scoring and Histopatholmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Combined final scores for each mouse range from 0 to 12, with the total score recorded in the final analysis. A CSS of 6 or greater is considered consistent with C. difficile colitis 12.…”

mentioning

confidence: 99%

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