Metabolic Influence of S. boulardii and S. cerevisiae in Cross-Kingdom Models of S. mutans and C. albicans

Recent studies highlight the potential of <i>Saccharomyces</i> species as probiotics due to their ability to modulate microbial interactions and reduce cariogenic activity, yet the underlying metabolic mechanisms remain unclear. This study investigates the cross-kingdom metabolic effects of <i>Saccharomyces boulardii</i> and <i>Saccharomyces cerevisiae</i> on the metabolic processes of <i>Streptococcus mutans</i> and <i>Candida albicans</i> using a metabolomics-based approach. Untargeted LC-MS/MS analysis was conducted to assess metabolites in a planktonic model, followed by metabolomic profiling and pathway analysis to identify key metabolic alterations. The results revealed that <i>S. boulardii</i> and <i>S. cerevisiae</i> demonstrated metabolic regulatory effects on <i>S. mutans</i> and <i>C. albicans</i>. Specifically, <i>S. boulardii</i> down-regulated 262 metabolites and up-regulated 168, while <i>S. cerevisiae</i> down-regulated 265 metabolites and up-regulated 168. Both yeast species down-regulated carbohydrate and amino acid metabolism in <i>S. mutans</i> and <i>C. albicans</i>, resulting in reduced biomolecule synthesis and a less acidic environment. <i>S. boulardii</i> and <i>S. cerevisiae</i> also up-regulated certain metabolic processes, including purine metabolism, suggesting a compensatory mechanism for nucleotide synthesis. Notably, dual regulatory effects were observed, where specific metabolites were simultaneously up-regulated and down-regulated, indicating complex metabolic crosstalk. These findings suggest that both <i>S. boulardii</i> and <i>S. cerevisiae</i> modulate microbial metabolism through a shared mechanism, offering potentials for dental caries prevention.