Saccharomyces cerevisiae 48338 Suppresses Antibiotic-Induced Clostridioides difficile Infection in a Murine Model

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis, driven by toxin-mediated epithelial injury and inflammation. While antibiotics such as vancomycin remain the primary treatment, they can further disrupt the gut microbiota and promote recurrence. Probiotics, including yeast strains, have emerged as potential adjunctive therapies for mitigating CDI. In this study, several Saccharomyces cerevisiae strains were evaluated for their probiotic potential, and strain 48338 was identified as the most promising candidate based on its gastrointestinal tolerance, auto-aggregation ability, and antioxidant activity. Using a CDI mouse model, we found that treatment with S. cerevisiae 48338 reduced disease severity, as reflected by lower clinical sickness scores. Quantitative PCR analysis confirmed that the expression of the toxin gene tcdA was significantly decreased following 48338 treatment, whereas total C. difficile burden remained unchanged. In addition, 48338 treatment might enhance intestinal barrier integrity by upregulating occludin gene expression and also might attenuate production of pro-inflammatory cytokines, particularly the expression of IL-1β. The strain also increased the proportions of Foxp3⁺ regulatory T cells and macrophages in both the spleen and mesenteric lymph nodes, as determined by flow cytometry, suggesting a shift towards an anti-inflammatory immune profile. Collectively, these findings suggest that the primary mechanism by which S. cerevisiae 48338 exerts its protective effect against C. difficile infection is not through direct reduction of C. difficile colonization, but primarily through modulation of the microbiome, host immune response, and maintenance of epithelial cell integrity. This study highlights the potential of yeast-based probiotics as adjunctive agents for the prevention or mitigation of CDI.