| Summary: | <i>Saccharomyces cerevisiae</i> var. <i>boulardii</i> (<i>Sb</i>) is currently receiving significant attention as a synthetic probiotic platform due to its ease of manipulation and inherent effectiveness in promoting digestive health. A comprehensive exploration of <i>Sb</i> and other <i>S. cerevisiae</i> strains (<i>Sc</i>) would shed light on the refinement and expansion of their therapeutic applications. This review aims to provide a thorough overview of <i>Saccharomyces</i> yeasts from their native health benefits to recent breakthroughs in the engineering of <i>Saccharomyces</i> yeasts as synthetic therapeutic platforms. Molecular typing and phenotypic assessments have uncovered notable distinctions, including the superior thermotolerance and acid tolerance exhibited by <i>Sb</i>, which are crucial attributes for probiotic functions. Moreover, parabiotic and prebiotic functionalities originating from yeast cell wall oligosaccharides have emerged as pivotal factors influencing the health benefits associated with <i>Sb</i> and <i>Sc</i>. Consequently, it has become imperative to select an appropriate yeast strain based on a comprehensive understanding of its actual action in the gastrointestinal tract and the origins of the targeted advantages. Overall, this review underscores the significance of unbiased and detailed comparative studies for the judicious selection of strains.
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