Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice.

Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 109 colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (SEM 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (SEM 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (SEM 0·73) UMPO/mg); nitrite concentration (control 37·00 (SEM 2·39) µm, 5-FU 59·04 (SEM 11·41) µm and 5-FU+S. boulardii 37·90 (SEM 5·78) µm); GSH concentration (control 477·60 (SEM 25·25) µg/mg, 5-FU 270·90 (SEM 38·50) µg/mg and 5-FU+S. boulardii 514·00 (SEM 38·64) µg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1ß by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C-X-C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying (control 25·21 (SEM 2·55) %, 5-FU 54·91 (SEM 3·43) % and 5-FU+S. boulardii 31·38 (SEM 2·80) %) and induced the recovery of intestinal permeability (lactulose:mannitol ratio: control 0·52 (SEM 0·03), 5-FU 1·38 (SEM 0·24) and 5-FU+S. boulardii 0·62 (SEM 0·03)). In conclusion, S. boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in intestinal mucositis induced by 5-FU.

Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice.

PURPOSE: Lactobacillus acidophilus is widely used for gastrointestinal disorders, but its role in inflammatory conditions like in chemotherapy-induced mucositis is unclear. Here, we report the effect of L. acidophilus on 5-fluorouracil-induced (5-FU) intestinal mucositis in mice. METHODS: Mice weighing 25-30 g (n = 8) were separated into three groups, saline, 5-FU, and 5-FU + L. acidophilus (5-FU-La) (16 × 10(9) CFU/kg). In the 5-FU-La group, L. acidophilus was administered concomitantly with 5-FU on the first day and alone for two additional days. Three days after the last administration of L. acidophilus, the animals were euthanized and the jejunum and ileum were removed for histopathological assessment and for evaluation of levels of myeloperoxidase activity, sulfhydryl groups, nitrite, and cytokines (TNF-α, IL-1ß, CXCL-1, and IL-10). In addition, we investigated gastric emptying using spectrophotometry after feeding a 1.5-ml test meal by gavage and euthanasia. Data were submitted to ANOVA and Bonferroni's test, with the level of significance at p < 0.05. RESULTS: Intestinal mucositis induced by 5-FU significantly (p < 0.05) reduced the villus height-crypt depth ratio and GSH concentration and increased myeloperoxidase activity and the nitrite concentrations compared with the control group. Furthermore, 5-FU significantly (p < 0.05) increased cytokine (TNF-α, IL-1ß, and CXCL-1) concentrations and decreased IL-10 concentrations compared with the control group. 5-FU also significantly (p < 0.05) delayed gastric emptying and gastrointestinal transit compared with the control group. All of these changes were significantly (p < 0.05) reversed by treatment with L. acidophilus. CONCLUSIONS: Lactobacillus acidophilus improves the inflammatory and functional aspects of intestinal mucositis induced by 5-FU.