Modulation of 5-fluorouracil activation of toll-like/MyD88/NF-κB/MAPK pathway by Saccharomyces boulardii CNCM 1-745 probiotic

Background and aim: Chemotherapy drugs that act via Toll-like receptors (TLRs) can exacerbate mucosal injury through the production of cytokines. Intestinal mucositis can activate TLR2 and TLR4, resulting in the activation of NF-kappa B. Intestinal mucositis characterized by intense inflammation is the main side effect associated with 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii CNCM I-745 (S.b) is a probiotic yeast used in the treatment of gastrointestinal disorders. The main objective of the study was to evaluate the effect of S.b treatment on the Toll-like/MyD88/NF-kappa B/MAPK pathway activated during intestinal mucositis and in Caco-2 cells treated with 5-FU. Methods: The mice were divided into three groups: saline (control), saline + 5-FU, and 5-FU + S.b (1.6 x 10(10) colony forming units/kg). After 3 days of S.b administration by gavage, the mice were euthanized and the jejunum and ileum were removed. In vitro, Caco2 cells were treated with 5-FU (1 mM) alone or in the presence of lipopolysaccharide (1 ng/ml). When indicated, cells were exposed to S.b. The jejunum/ileum samples and Caco2 cells were examined for the expression or concentration of the inflammatory components. Results: Treatment with S.b modulated the expressions of TLR2, TLR4, MyD88, NF-kappa B ERK1/2, phospho-p38, phospho-JNK, TNF-alpha, IL-1 beta, and CXCL-1 in the jejunum/ileum and Caco2 cells following treatment with 5-FU. Conclusion: Toll-like/MyD88/NF-kappa B/MAPK pathway are activated during intestinal mucositis and their modulation by S.b suggests a novel and valuable therapeutic strategy for intestinal inflammation.