Abstract Background Several studies have shown altered intestinal fungal composition and diversity in IBD, suggesting an immunomodulatory role. However, data from Latin American populations remain limited. Our study aim to characterise the fungal microbiota profile in Chilean patients with active and inactive ulcerative colitis (UC), compared with healthy controls. Methods Intestinal mucosal wash samples from 101 participants (active UC: 30, inactive UC: 38, healthy controls: 33) were analysed through ITS1/ITS2 region sequencing. Alpha diversity was assessed using Chao1 and Shannon indices (Wilcoxon test, p 0.05), and beta diversity was evaluated by NMDS based on Unweighted UniFrac distances and PERMANOVA (1,000 permutations, FDR 0.05). Differential abundance analyses (Wilcoxon and Kruskal–Wallis tests) and biomarker identification (LEfSe, LDA2) were performed.Bulk RNA-seq of 30 samples was analysed with DESeq2 (FDR ≤ 0.05; log2FC ≥ 1 or ≤ −1), and gene expression was correlated with fungal abundance at genus and species levels. Results Fungal richness (Chao1) was lower in UC patients compared to controls, while Shannon diversity showed no significant difference. Beta diversity revealed significant group differences by Unweighted UniFrac (PERMANOVA). The Ascomycota/Basidiomycota ratio—a widely used ecological marker reflecting the balance between dominant fungal phyla—was decreased in UC, with the lowest values in active disease. This reduction suggests a dysbiotic shift toward Ascomycota dominance and loss of Basidiomycota-associated commensal diversity, consistent with prior reports. No differences were observed at the family level, but genus- and species-level shifts were evident (Figure 1a), with decreased Nakaseomyces, Yarrowia, and Filobasidium, and increased Rhodotorula araucariae and Pichia fermentans in active UC. Penicillium penicilloides was enriched in active UC versus controls. At the species level, F. chernovii, R. araucariae, and P. fermentans (Figure 1b) all correlated positively with inflammatory gene expression and with each other, suggesting an association with mucosal inflammation. Conclusion The intestinal mycobiota of Chilean UC patients showed reduced richness and a lower Ascomycota/Basidiomycota ratio, indicating fungal imbalance. Reduced Yarrowia may indicate loss of protective fungi, while decreased Filobasidium and increased Rhodotorula araucariae, Pichia fermentans, and Penicillium correlated with inflammation. Filobasidium and Pichia patterns mirrored European reports, whereas Penicillium associated with disease activity as in Chinese but not European cohorts, underscoring population-specific fungal signatures in UC. References: Catalán-Serra I, Thorsvik S, Beisvag V, et al. Fungal Microbiota Composition in Inflammatory Bowel Disease Patients: Characterization in Different Phenotypes and Correlation With Clinical Activity and Disease Course. Inflamm Bowel Dis. 2024;30(7):1164-1177. doi:10.1093/ibd/izad289 van Thiel IAM, Rahman S, Hakvoort TBM, et al. Fecal Filobasidium Is Associated with Clinical Remission and Endoscopic Response following Fecal Microbiota Transplantation in Mild-to-Moderate Ulcerative Colitis. Microorganisms. 2022;10(4):737. Nooman MU, Al-Kashef AS, Rashad MM, Khattab AEA, Ahmed KA, Abbas SS. Sophorolipids produced by Yarrowia lipolytica grown on Moringa oleifera oil cake protect against acetic acid-induced colitis in rats: impact on TLR-4/p-JNK/NFκB-p65 pathway. J Pharm Pharmacol. 2023;75(4):544-558. Qiu X., Ma J., Jiao C., Mao X., Zhao X., Lu M., Wang K., Zhang H. Alterations in the mucosa-associated fungal microbiota in patients with ulcerative colitis. Oncotarget. 2017; 8: 107577-107588. Conflict of interest: Dr. Pérez, Tamara: No conflict of interest Valdes, Ivania: No conflict of interest Ascui, Gabriel: No conflict of interest Hernandez-Rocha, Cristian: No conflict of interest Segovia, Roberto: No conflict of interest Pavez, Carolina: No conflict of interest Candia, Roberto: No conflict of interest Hernandez, Elisa: No conflict of interest Silva, Veronica: No conflict of interest Arriagada, Elizabeth: No conflict of interest Azocar, Lorena: No conflict of interest Juan Francisco, Miquel: No conflict of interest Marki, Alex: No conflict of interest Riquelme, Erick: No conflict of interest Alvarez-lobos, Manuel: No conflict of interest Sharma-Oates, Archana: No conflict of interest
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