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 (16x10(9) 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 20min 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 173 (sem 037) ultrastructural MPO (UMPO)/mg, 5-FU 737 (sem 177)UMPO/mg and 5-FU+S. boulardii 415 (sem 073)UMPO/mg); nitrite concentration (control 3700 (sem 239)m, 5-FU 5904 (sem 1141)m and 5-FU+S. boulardii 3790 (sem 578)m); GSH concentration (control 47760 (sem 2525)g/mg, 5-FU 27090 (sem 3850)g/mg and 5-FU+S. boulardii 51400 (sem 3864)g/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF- and IL-1 by 4892 and 3221% in the jejunum and 3892 and 6179% 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 2521 (sem 255)%, 5-FU 5491 (sem 343)% and 5-FU+S. boulardii 3138 (sem 280)%) and induced the recovery of intestinal permeability (lactulose:mannitol ratio: control 052 (sem 003), 5-FU 138 (sem 024) and 5-FU+S. boulardii 062 (sem 003)). In conclusion, S. boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in intestinal mucositis induced by 5-FU.