Mechanism and therapeutic effects of Saccharomyces boulardii on experimental colitis in mice

Inflammatory bowel disease (IBD) is a type of chronic inflammatory disturbance that affects a number of individuals worldwide; the precise mechanism is unclear and treatment is frequently insufficient to maintain patients in remission. Saccharomyces boulardii is a thermophilic, non-pathogenic yeast that may be administered for prophylaxis and treatment of a variety of diarrheal diseases. Recent clinical studies have demonstrated that it may have a role in IBD; however, the mechanism of action is unclear. The hypoxia-inducible factors (HIFs) are ubiquitously expressed regulators of cellular adaptation to hypoxia and are central to the adaptive and inflammatory responses of cells of the intestinal mucosa in patients with IBD. The present study aimed to investigate the effects of S. boulardii on dextran sulfate sodium (DSS)-induced colitis in mice and the effects of S. boulardii on HIFs. Mice were divided into five groups (n=10 mice/group): i) Control; ii) DSS; iii) S. boulardii (Sb) + DSS; iv) normal saline (NS) + DSS; and v) Sb. For 14 consecutive days, mice from the Sb+DSS and Sb groups were given S. boulardii suspension in saline (150 mg/kg/day; final volume 0.2 ml) by oral gavage. The NS+DSS group received the same volume of NS by gavage. The Control mice received water only. From day 8 to day 14, 3.5% DSS was added to the drinking water of the DSS, Sb+DSS and NS+DSS groups to induce acute colitis. Body weight decreased and disease activity index and histological score increased in mice with DSS-induced colitis. Oral administration of S. boulardii reduced DSS-induced weight loss, ameliorated the histological damage and protected the colon barrier in mice with DSS-induced colitis. The expression of HIF-1 and HIF-2 in colon tissues was measured by reverse transcription-quantitative polymerase chain reaction, immunoblotting and immunohistochemistry. The increase in HIFs in the colon induced by DSS was significantly inhibited by S. boulardii treatment. The expression levels of several epithelial-mesenchymal transition (EMT) markers and of vascular endothelial growth factor (VEGF) that are regulated by HIFs were measured. S. boulardii reduced EMT and decreased expression of VEGF that was induced by DSS treatment. These results indicated that treatment with S. boulardii ameliorated DSS-induced colitis, partly through downregulation of HIF-1 and HIF-2.