Insights into the Relevance of the Interaction between Colorectal Cancer and Gut Microbiota-Derived Metabolites

Colorectal cancer (CRC) is strongly associated with gut microbial dysbiosis, characterized by increases in Escherichia coli, Enterococcus faecalis, and Bacteroides spp., and reduction in short chain fatty acid producing taxa such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Roseburia. These shifts parallel metabolomic disturbances, including decreased butyrate and immune dysregulation. Several microbial and metabolic markers such as Akkermansia, Faecalibacterium, butyrate, tryptophan metabolites, and sarcosine have demonstrated strong diagnostic performance, with area under the receiver operating characteristic curve (AUC) values commonly ranging from 0.80 to 0.93 in CRC prediction models. This review integrates current evidence for microbes and metabolite interactions that drive CRC progression and summarizes biomarker studies employing high AUC microbial and metabolite signatures for early detection and patient stratification. We further highlight phytochemicals, including resveratrol, curcumin, and quercetin which mitigate CRC by modulating cyclooxygenase-2 activity, macrophage polarization, inflammatory cytokine signaling, and metabolic pathways, as well as the restoration of beneficial gut microbial communities. These insights support the advancement of microbiome targeted and metabolite informed approaches for CRC risk assessment, diagnosis, and therapeutic development.