P1229 The Role and Niche-Specific Adaptation of Malassezia in patients with Ulcerative colitis

Background Accumulating evidence has underscored the role of gut fungal microbiota (mycobiota) in the development of inflammatory bowel disease. We aimed to isolate a Malassezia strain directly from the human intestine mucosal surface from the patients with ulcerative colitis (UC) and investigated its genome and virulence in comparison with the same fungal species isolated from the human skin. Methods Mucosal lavage samples were collected separately from colonic areas with and without inflammation in patients with UC. Samples from healthy individuals (HT) were obtained in the same manner as from patients with UC at sigmoid or descending colon. Skin samples were taken from HT in our previous work. DNA was extracted from these lavage samples, and fungal isolation was conducted using PCR amplification with ITS4 and ITS5 primers. Comprehensive analysis and comparison of the genomes, transcriptomes, and virulence between M. globosa gut isolates and those of M. globosa strains isolated from the skin were performed. To determine the contribution of M. globosa gut isolates to exacerbating inflammation, 1107 fungal cells were orally gavaged to DSS-induced colitis mouse model for three days. Results Total 56 and 11 intestinal water-lavage samples from 29 UC patients and 11 HT were obtained respectively. The α- and b-diversities of mycobiota showed no significant differences between the groups, patients with UC vs. HT or the sites with inflammation vs. non-inflammation of the patient with UC. Malassezia was the fifth most frequently found fungal genus throughout the samples, and live fungal strains belong to 28 and 7 different species were isolated from the patients with UC and HT, respectively. The patients with UC tend to have higher frequency of M. globosa and M. restricta than HT in their gut mucosal surface with inflammation. Whole genome sequencing showed no specific genomic characteristics between gut-isolated M. globosa and skin-isolated M. globosa. However, gut-isolated M. globosa were suffered more from the higher oxygen levels than the skin isolates in different oxygen concentrations. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines, including TNF-a, IL-6, IL-12p40, IL-1b, and IL-18, while the skin isolates showed no difference compared to the negative control (Figure). Conclusion Our data shed new light on the pivotal role of M. globosa in the pathogenesis of UC, highlighting the potential influence of niche-specific adaptations on the virulence of this fungus. These findings provide critical insights into the complex interplay between the member of the gut mycobiota and host health.