Saccharomyces boulardii (S. boulardii) is a non-pathogenic biotherapeutic agent, widely prescribed in a lyophilized form in many countries over the world. S. boulardii acts as a shuttle liberating effective enzymes, proteins and trophic factors during its intestinal transit that improve host immune defenses, digestion, and absorption of nutrients. In addition, S. boulardii secretes during its intestinal transit polyamines, mainly spermine and spermidine that regulate gene expression and protein synthesis. In this review, we will focus on the interactions of the yeast with the host intestinal mucosa.