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...

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Published in:	British journal of nutrition Vol. 111; no. 9; pp. 1611 - 1621
Main Authors:	Justino, Priscilla F. C., Melo, Luis F. M., Nogueira, Andre F., Costa, Jose V. G., Silva, Luara M. N., Santos, Cecila M., Mendes, Walber O., Costa, Marina R., Franco, Alvaro X., Lima, Aldo A., Ribeiro, Ronaldo A., Souza, Marcellus H. L. P., Soares, Pedro M. G.
Format:	Journal Article
Language:	English
Published:	Cambridge, UK Cambridge University Press 14-05-2014
Subjects:	Animals Anti-Inflammatory Agents, Non-Steroidal - immunology Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Biological and medical sciences Cytokines - metabolism Disease Models, Animal Down-Regulation Feces - chemistry Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Gastric Emptying Gastrointestinal Agents - immunology Gastrointestinal Agents - therapeutic use Gastrointestinal diseases Gastrointestinal tract Glutathione - metabolism Histopathology Ileum - immunology Ileum - metabolism Ileum - microbiology Ileum - pathology Intestinal Absorption Intestinal Mucosa - immunology Intestinal Mucosa - metabolism Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Jejunum - immunology Jejunum - metabolism Jejunum - microbiology Jejunum - pathology Male Mice Microbiology Mucositis - diet therapy Mucositis - immunology Mucositis - metabolism Mucositis - microbiology Neutrophil Infiltration Nitric Oxide - metabolism Permeability Peroxidase - metabolism Phenols Prebiotics Probiotics Random Allocation Rodents Saccharomyces - growth & development Saccharomyces - immunology Saccharomyces boulardii Spectrophotometry Vertebrates: anatomy and physiology, studies on body, several organs or systems Probiotics Saccharomyces boulardii Intestinal mucositis Inflammation 5-Fluorouracil Ascomycota Probiotic Mucositis Nutrition Digestive system Rodentia Gut Gastrointestinal Fungi Vertebrata Mammalia Treatment Mouse Dysfunction Animal Fluorouracil
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Summary:	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-1β 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0007-1145 1475-2662
DOI:	10.1017/S0007114513004248