Live Malassezia strains from the mucosa of patients with ulcerative colitis: pathogenic potential and environmental adaptations

Abstract

The human gut contains a diverse range of microorganisms, including bacteria, viruses, protozoa, and fungi. Although research has predominantly focused on bacterial populations, emerging evidence highlights the significant role of the gut mycobiota, particularly in the context of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease. This study investigates the intestinal mucosal mycobiota of UC patients, aiming to isolate and characterize live Malassezia fungal strains from the gut mucosa. Our analysis confirmed the presence of Malassezia in the intestinal mucosal layer of UC patients, with live Malassezia globosa strains being successfully isolated. As Malassezia is generally associated with the skin, the genomic and transcriptomic profiles and virulence of the M. globosa gut isolates were compared with those of the skin isolates. While both gut and skin isolates of M. globosa shared high genomic similarity, transcriptomic analysis revealed distinct responses to oxygen levels, suggesting niche-specific adaptation. Compared with the skin isolates, the gut isolates exhibited higher virulence in a dextran sulfate sodium-induced mouse colitis model, resulting in more severe disease, reduced survival rates, and elevated proinflammatory cytokine levels in the host. Our findings highlight the potential role of M. globosa in the pathogenesis of IBD and underscore the importance of niche-specific adaptations in fungal virulence.IMPORTANCEMalassezia fungi predominantly reside on human skin and are associated with several skin diseases, such as seborrheic dermatitis. They have also been implicated in various other diseases, including inflammatory bowel disease (IBD). While Malassezia DNA has been detected in many fungal microbiome studies using fecal samples, no previous research had isolated live Malassezia strains from the gut or confirmed that live Malassezia cells reside within the gut environment. In this study, we successfully isolated live Malassezia globosa strains from the gut mucosal surface of ulcerative colitis patients and compared them to M. globosa skin isolates. Our results revealed significant differences in pathogenicity between the gut and skin isolates and suggest the important role of M. globosa in the gut and its involvement in IBD.