Abstract
BackgroundProbiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle)-induced colitis. The spore forming probiotic strain Bacillus Coagulans GBI-30, 6086 (BC30) has demonstrated anti-inflammatory and immune-modulating effects in vitro. Our goal was to determine if BC30 improved C. difficile-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline) or BC30 (2 × 109 CFU per day). Mice in the C. difficile groups received an antibiotic mixture (study days 5 to 8 in the drinking water), and clindamycin (10 mg/kg, i.p., on study day 10). The C. difficile strain VPI 10463 was given by gavage at 104 CFU to induce colitis on day 11. On day 16, stools and colons were collected for further analyses.ResultsAll mice treated with BC30 survived on study day 13, while two mice treated with vehicle did not survive. On day 12, a significant difference (p = 0.0002) in the percentage of mice with normal stools (66.7%) was found in the BC30/C. difficile group, as compared to the vehicle/C. diffcile group (13.0%). On study day 16, 23.8% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0187). On this day, the stool consistency score for the BC30/C. difficile group (1.1 ± 0.2) was significantly lower (p < 0.05) than for the vehicle/C. difficile cohort (1.9 ± 0.2). BC30 modestly attenuated the colonic pathology (crypt damage, edema, leukocyte influx) that was present following C. difficile infection. Colonic MIP-2 chemokine contents (pg/2 cm colon) were: 10.2 ± 0.5 (vehicle/no C. difficile), 24.6 ± 9.5 (vehicle/C. difficile) and 16.3 ± 4.3 (BC30/C. difficle).ConclusionThe probiotic BC30 improved some parameters of C. difficile-induced colitis in mice. BC30 prolonged the survival of C. diffiicle infected mice. Particularly, this probiotic improved the stool consistency of mice, in this infectious colitis model.
Highlights
Probiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle)-induced colitis
BC30 prolongs mouse survival after the administration of C. difficile Figure 1 shows an overview of the key events associated with the C. difficile induced colitis model that was used for this study
By day 14, 21/23 mice survived in the BC30/C. difficile treatment group, while 23/26 mice survived in the Vehicle/C. difficile treatment group
Summary
Probiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle)-induced colitis. The C. difficile strain VPI 10463 was given by gavage at 104 CFU to induce colitis on day 11. Previous data suggests that toxin A can activate the nuclear factor-kappa B (NF-B) signal transduction system in monocytes and colonic epithelial cells [4,5]. This activation of NF-B leads to secretion of a key pro-inflammatory chemokine (IL-8) and subsequently to neutrophil influx. Some clinical studies have focused on combined treatment with vancomycin and probiotics such as Saccharomyces boulardii for recurrent disease [8,9,10,11]. Initial treatment regimens with probiotics, or their use for prevention of recurrent disease, may be attractive as part of the overall therapeutic strategy for CDAD [8,9,10,11]
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