Exploring the association of gut mycobiome composition with colorectal cancer, colorectal polyps, and healthy subjects in malaysian cohorts / Aisyah Binti Yunus

Faculty of Industrial Sciences and Technology

Thesis (Master of Science) -- Universiti Malaysia Pahang – 2025

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Colorectal cancer (CRC) is a significant public health concern and ranks among the leading causes of cancer-related mortality worldwide. Although the role of the gut microbiome in CRC development has been thoroughly investigated, the specific contribution of the gut mycobiome, particularly fungal communities, remains underexplored. This study aimed to investigate and compare the gut mycobiome composition in CRC patients, individuals with pre-CRC polyps, and healthy controls within Malaysian cohorts, and to identify potential fungal biomarkers for CRC detection. Biopsy samples from 77 subjects underwent high-throughput amplicon sequencing targeting the ITS1 region. Genomic DNA extraction yielded concentrations ranging from 12.2 to 80.5 ng/μL, with an average of 41.29 ng/μL. Taxonomic profiling revealed a comprehensive analysis of fungal taxa at both the phylum and genus levels. Among all groups, Ascomycota and Basidiomycota were identified as the most prevalent phyla. At the genus level, Mortierella was abundant in polyp patients, while Aspergillus was more prevalent in CRC patients. Saitozyma was more prevalent in healthy individuals compared to CRC and polyp patients. Alpha-diversity analysis using the Chao1 index revealed significant differences in fungal richness across the CRC, polyp, and healthy groups (p < 0.05), indicating an impact of disease status on gut fungal diversity. Betadiversity analysis demonstrated distinct fungal compositions across the cohorts, though the differences were not statistically significant (p > 0.05), suggesting the influence of additional contributing factors. LEfSe analysis identified H. werneckii as a potential fungal marker for CRC patients, while other taxa, such as Saitozyma podzolica, Aspergillus versicolor, S. etchellsii, V. victoriae, Zopfiella sp., P. niemeijerarum, U. isabellina, E. thailandicum, and L. cordylinicola, were associated with healthy individuals. Additionally, dietary intake analysis revealed that CRC patients had the highest protein intake, exceeding the Recommended Nutrient Intake (RNI). A correlation was observed between dietary patterns and the prevalence of specific fungal taxa, indicating a possible interaction between diet and gut fungal composition. Despite providing novel insights into the role of gut mycobiome in CRC pathogenesis, this study has several limitations which include the use of a cross-sectional design, a relatively small sample size, and reliance on amplicon sequencing, limiting functional interpretation. Further research should focus on expanding the sample size and employing functional assays to explore the mechanistic roles of key fungal species in CRC development.