Gut fungal landscape in colorectal cancer and its cross-kingdom interplay with gut microbial ecology

ABSTRACT:

Background: The gut microbiota is a key hallmark of tumor and plays a central role in colorectal cancer (CRC). However, the contribution of gut fungi, an important community of gut microbes, remains substantially understudied in CRC.

Objective: To characterize the gut fungal landscape in CRC and elucidate its associations with bacterial communities, metabolites, and trace elements.

Methods: We conducted metagenomic sequencing on fecal samples from three cohorts: healthy controls (n = 401), colorectal polyp patients (n = 162), and CRC patients (n = 253). The fungal genomic data from NCBI database (PRJNA833221) was served as the reference for annotating gut fungi. Metabolites and trace elements were quantified via liquid chromatography and inductively Coupled Plasma Mass Spectrometry (ICP-MS), respectively. Fungal diversity and compositional differences were analyzed across groups. A random forest model was trained to discriminate healthy controls from intestinal disease groups (polyps and CRC) based on microbial biomarkers, with an ablation study optimizing co-marker selection. Structural equation modeling (SEM) was employed to dissect interactions among fungi, bacteria, metabolites, and trace elements.

Results: CRC patients exhibited increased fungal diversity at the genus level. Seven fungal genera displayed differential abundance across three groups: Rhizopus was specifically enriched in CRC, whereas Sporisorium, Cladosporium, Aureobasidium, Zygoascus, and Meyerozyma were enriched in polyps. Ablation study identified an optimal 31-microbial-marker panel (28 bacterial and 3 fungal species) that effectively distinguished intestinal disease groups (AUC = 0.89). SEM analysis identified three fungal markers—Penicillium citrinum, Penicillium sp. PG10607D, and Rhizopus stolonifera—that influence bacterial-metabolite-trace element networks through distinct correlations.

Conclusion: This study plots the first gut fungal atlas for CRC and reveals complex cross-kingdom interactions involving fungi, bacteria, metabolites, and trace elements, providing new insights into CRC research.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS12776 | MetaboLights | 2025-07-26

REPOSITORIES: MetaboLights