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

The gut microbiota is a key hallmark of colorectal cancer (CRC), yet gut fungi remain understudied. We characterized the gut fungal landscape and its associations with bacteria, metabolites, and trace elements in CRC using fecal samples from healthy controls (<i>n</i> = 401), colorectal polyp patients (<i>n</i> = 162), and CRC patients (<i>n</i> = 253). Fungal annotation was performed using genomic data from NCBI (PRJNA833221) as reference. Fungal diversity increased in CRC patients, with seven genera showing differential abundance. <i>Rhizopus</i> was specifically enriched in CRC, while <i>Sporisorium</i>, <i>etc</i>. enriched in polyps. Ablation study identified an optimal 31-microbial-marker panel (28 bacteria and three fungi) that effectively distinguished intestinal disease groups (AUC = 0.89). Structural equation modeling revealed three fungal markers-<i>Penicillium citrinum</i>, <i>Penicillium</i> sp. <i>PG10607D</i>, and <i>Rhizopus stolonifera</i>-that influence bacterial-metabolite-trace element networks. This study delineates the gut fungal atlas in CRC and reveals complex cross-kingdom interactions, offering new insights into CRC pathogenesis.