Abstract
Background: Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition characterized by recurrent intestinal inflammation and complications. Despite extensive research on bacterial dysbiosis in IBD, the role of the gut mycobiome remains largely unexplored, particularly in surgical tissue specimens. Methods: In this study, we performed a comprehensive analysis of the intestinal fungal communities in surgical resections obtained from 20 patients with UC and 30 patients with CD, with non-IBD resections serving as controls. Fungal DNA was extracted and the internal transcribed spacer (ITS) region was amplified and sequenced using high-throughput Illumina technology. RNA from surgical resections from both non-IBD and IBD patients was obtained and the expression of pro-inflammatory and profibrotic genes was analyzed by real-time quantitative polymerase chain reaction. Results: Bioinformatic analysis revealed modest changes in fungal diversity in UC resections compared with those from controls. However, CD specimens exhibited significant alterations in mycobiome composition, including an increased abundance of Malassezia, specifically Malassezia globose, alongside a reduction in Yarrowia lipolytica. Moreover, stratification of CD into complicated phenotypes (B2 stricturing vs B3 penetrating) identified distinct fungal signatures capable of discriminating between these clinical phenotypes. Correlation analyses revealed a direct association between the mycobiome and intestinal inflammation and fibrosis, in parallel with several interactions between fungal and bacterial species, further reporting interkingdom interactions between both microbial communities. Conclusions: These results underscore the potential of fungal biomarkers in elucidating IBD pathogenesis and its associated complications, which opens up promising avenues for targeted therapeutic strategies.