PS11-4: Population genomics of Saccharomyces cerevisiae human isolates reveals adaptation to the gastrointestinal tract

Despite in-depth knowledge of the genetic, molecular and phenotypic traits regulating the physiology of Saccharomyces cerevisiae, the forces shaping its origin and evolution are still debated. S. cerevisiae has been associated to human activities so deeply to harbour the notion of being a domesticated organism. The quest for the ecological niches of S. cerevisiae has led to examine its population structure, and to classify with respect to the source and the type of human activity from which it derived. Since human exposure to fungi is constant, recent studies have begun to note that the mycobiota, the commensal fungal community, is a significant player in host-microbe interactions. A recent hypothesis is that human environment-associated S. cerevisiae give rise to clinical strains causing colonization/infection. A few studies investigated fungal communities in chronic inflammation, especially in Inflammatory Bowel Diseases (IBD), and the production of anti-Saccharomyces cerevisiae antibodies (ASCA), one of the diagnostic markers of Crohn’s disease (CD). Here we present the genetic structure of a previously unknown populations of yeasts associated with human gut and especially with pediatric CD patients. S. cerevisiae strains isolated from the human gut showed clonal expansion and a unique cell wall composition with increased galactose and decreased mannose, thus suggesting selection and adaptation to the gut environment. A systems level approach, combining whole genome sequencing with immunephenotyping of gut isolates, discovered selection on genes involved in sporulation and cell wall remodeling as crucial for the evolution of S. cerevisiae in the gut. Classifying gut strains according to their immunomodulatory properties, we discovered a set of genetically homogeneous isolates capable of inducing anti-inflammatory signals via regulatory T cell proliferation and another group of isolates with a mosaic genome, eliciting inflammatory immune response. Sporulation is associated with strain-specific differences in the cytokine pattern and with ASCA marker in CD patients, thus reflecting the yeast’s ability to induce different inflammatory responses. We provide evidence that cell wall remodeling and sporulation ability is crucial for live in the gut and therefore we propose the role of the human gut in shaping S. cerevisiae evolution.