Transcriptomic combined physiological analysis illuminated the gastrointestinal stress mechanism of <i>Saccharomyces boulardii</i>

Gastrointestinal stress significantly influences the functionality and survival of food-derived probiotics after ingestion. <i>Saccharomyces boulardii</i> is widely recognized for its remarkable resilience to gastrointestinal challenges, yet the molecular mechanisms underlying this tolerance remain incompletely understood. In this study, an integrated physiological and transcriptomic approach was employed to elucidate the adaptive responses of <i>S. boulardii</i> to gastrointestinal stress. Under gastrointestinal stress conditions, cell morphology changes, intracellular reactive oxygen species levels increase, and the activity of antioxidant enzyme systems also increases. Notably, the effects of intestinal fluid stress on cellular integrity were more severe compared to gastric fluid stress. Transcriptomic analysis revealed extensive changes in gene expression, particularly in pathways related to carbon metabolism and ribosomal biogenesis. KEGG pathway enrichment identified 15 differentially expressed genes associated with carbohydrate transport and amino acid metabolism, predominantly up-regulated. Furthermore, 26 genes involved in ribosome biosynthesis were significantly up-regulated, especially under intestinal fluid stress. These findings highlight the critical role of ribosome biogenesis and metabolic adaptations in the stress tolerance of <i>S. boulardii</i>. The insights of this study contribute to the development of strategies for enhancing the survival and efficacy of probiotics in functional foods and therapeutic applications.