Project description:The human gut is inhabited by a complex ecosystem of microorganisms, encompassing bacteria, viruses, protozoa, and fungi. Recent research has illuminated the significance of the gut fungal microbiota (mycobiota) in shaping host immunity and influencing the onset and progression of various human diseases. While most investigations into gut microbiota have centered on bacteria, accumulating evidence has underscored the role of mycobiota in the development of inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD). In this study, we present the isolation of the live Malassezia globosa strains from the intestinal mucosa of UC patients for the first time. We provide a comprehensive analysis of the characteristics and virulence of this fungus. Malassezia, primarily known to inhabit human skin, prompted us to compare the genomes, transcriptomes, and virulence of M. globosa gut isolates with those of M. globosa strains isolated from the skin. This comparative analysis aimed to discern potential niche-specific adaptations of the fungus. Our findings reveal a striking disparity in the pathogenicity of M. globosa isolated from the gut compared to its skin counterpart. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines. Additionally, transcriptome analysis indicated that gut isolates of M. globosa display heightened sensitivity to normoxia compared to their skin-isolated counterparts, suggesting adaptation to the hypoxic conditions prevalent in the intestinal mucosal environment
