Microbiome Engineering Using Saccharomyces Boulardii

Saccharomyces boulardii has great potential for use as a chassis for microbiome engineering due to its high resistance to environmental stress, well-developed genetic tools, and the ability to secrete recombinant proteins in the intestine. As oral feeding of lysozyme has been reported to change the gut microbiome, we engineered S. boulardii to secrete human lysozyme, and investigated the changes in the gut microbiome and fecal metabolites in response to the administration of the engineered probiotic yeast into mice. Administration of S. boulardii changed the gut microbiome structure by promoting the growth of clostridia and increasing the diversity of strains. The human lysozyme secreted by S. boulardii in the intestine resulted in a unique gut microbiome structure through selective growth of specific microorganisms. Our study identified changes in the gut microbiome by administering wild-type S. boulardii in mice to healthy mice based on long-read sequencing and demonstrated that a recombinant protein secreted by engineered S. boulardii in the intestine could change the microbiome. Our results provide valuable information for the development of bio-therapeutics using engineered S. boulardii that changes the gut microbiome and host physiology.