Differential analysis of microbial profiles in colorectal cancer reveals modulations corresponding to immune subtypes

The proximity of the gut microbiome to the tumor microenvironment (TME) in colorectal cancer (CRC) presents a unique ecological niche. A systematic study of tumor-microbiome interactions will facilitate a deeper understanding of the heterogeneity in immune response and clinical outcomes in CRC. Previous studies have identified specific microbial species such as Fusobacterium nucleatum, pks⁺ Escherichia coli, and enterotoxigenic Bacteroides fragilis as contributors to CRC initiation and progression. However, the extent to which interactions between the microbiome and immune landscape affect prognosis and tumor heterogeneity remains poorly understood. To address this, immune subtypes from The Cancer Genome Atlas (TCGA) were integrated with microbial profiles from The Cancer Microbiome Atlas (TCMA) to examine the relationship between immune subtypes and the tumor microbiome in CRC. A cohort of 631 TCGA CRC cases with clinical, microbial and immune subtype data was analyzed. Differential abundance analysis indicated significant associations between specific taxa and immune subtypes. We demonstrate that pathogenic genera such as Selenomonas, Butyricimonas and Centipeda are significantly enriched (p_adjusted < 0.05) in the C2 IFN-ɣ dominant subtype. Our findings show that the abundance of pathogenic genera may play a critical role in driving the paradoxically poorer survival observed in CRC patients with the C2 subtype.