Bridging the yeast environments of cell culture production and the human gut: Adaptation as key to unlock high pharmaceutical and probiotic functionality

Research Project, 2022 – 2024

Microbial cells receive attention as probiotics due to health benefits and contribution to gut health. The yeast Saccharomyces boulardii is marketed as a pharmaceutical to prevent and treat diarrhea and as a probiotic with claimed effects towards digestive tract problems. Pivotal for the use of S. boulardii is that it after cell culture production exhibit high cellular activity of the intended use in the digestive tract. However, studies point out limited efficiency of many probiotics. Significant phenotypic diversity in subpopulations following cell culture production may explain the lack of efficiency. The underlying hypothesisis for the proposed project is that if the cells are cultivated under conditions that dominate in the gut, more robust cell performance will result. Cellular quality will be assessed as probiotic and pharmaceutical functionality including cell viability in digestive tract conditions. We will study how the physiology of S. boulardii depends on conditions prevailing in the digestive tract to map the phenotypic plasticity of the yeast. We will combine this information with investigations of cellular quality the after using different cell culture production conditions to adapt the cells to increase the cellular quality. We will compare the transcriptional profile of improved cell cultures using RNA-sequencing of the entire populations as well as single-cell levels to profile the effects at subpopulations to gain understanding of the phenotypic plasticity.