Microbial influences on immune modulation and colorectal cancer progression through combined transcriptomic and microbiomic analysis

Schematic representation of the distinct tumor microenvironment characteristics in CA1 and CA2 subtypes. CA1 illustrates an immune-active tumor microenvironment characterized by elevated infiltration of immune cells, particularly CD8 + T cells and macrophages, and enhanced IFN-γ signaling. This subtype shows enrichment of specific bacterial species (including P. gingivalis and B. fragilis) that contribute to immunomodulation through metabolic pathways such as γ-aminobutyric acid (GABA) and butanoate metabolism. Despite high immune activity, CA1 exhibits a poor prognosis, potentially linked to immune exhaustion, manifested by high expression of PD-1, CTLA-4, LAG-3, and TIM-3. CA2 depicts an immune-suppressed microenvironment featuring reduced immune cell infiltration, lower inflammatory signatures, and a distinct microbial composition dominated by health-associated bacteria. This tumor phenotype shows better overall survival even with reduced immune activity. Arrows indicate key molecular interactions, with solid lines representing direct effects and dashed lines indicating indirect modulation.