Arianette Campos

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, and increasing incidence among younger adults highlights the need for improved prevention strategies Although localized disease is often treatable, many tumor-promoting mechanisms occur before symptoms become clinically apparent. The gut microbiome has emerged as an important contributor to CRC biology because it regulates mucosal immunity, inflammatory signaling, and epithelial homeostasis Diet also shapes microbial composition and alters the metabolites to which the colonic epithelium is exposed. Therefore, dysbiosis may contribute to tumor development through bacterial signaling pathways and microbial metabolites that alter host-cell function While associations between microbiome composition and CRC risk are well described, the specific mechanisms by which microbes either promote or suppress tumor progression remain incompletely understood. Mechanistic studies identifying how bacteria influence oncogenic signaling and anti-tumor immunity may help identify actionable prevention targets.

Objective: This narrative review examined how the gut microbiome contributes to colorectal cancer progression and explored microbiome-based prevention strategies targeting bacterial signaling, epithelial pathways, and anti-tumor immunity.

Search Methods: An online literature search was conducted using the PubMed database from 2018 to 2024. Search terms and MeSH keywords included “colorectal cancer,” “gut microbiome,” “Fusobacterium nucleatum,” “Annexin A1,” “Wnt/β-catenin,” “short-chain fatty acids,” “bile acids,” and “CD8 T-cell function.” Primary studies highlighted in the presentation were selected for their mechanistic focus on microbial signaling pathways and immune regulation in CRC.

Results: Studies demonstrate that Fusobacterium nucleatum actively promotes CRC progression through bacterial-host signaling interactions rather than passive tumor association The FadA adhesin expressed by F. nucleatum binds E-cadherin on colorectal cancer cells and induces expression of Annexin A1, which amplifies Wnt/β-catenin signaling and promotes proliferative pathways including Cyclin D1 activation Importantly, this proliferative effect was selective to malignant colorectal cancer cells and was not observed in precancerous adenoma cells Additional studies demonstrated that beneficial microbial metabolites, particularly short-chain fatty acids (SCFAs), enhance anti-tumor immunity by increasing antigen-presentation machinery and chemokine signaling involved in cytotoxic T-cell recruitment In contrast, microbiota-modified bile acids such as deoxycholic acid suppress CD T-cell effector function through inhibition of CNFAT signaling, thereby weakening anti-tumor immune responses and promoting tumor growth

Conclusion: The gut microbiome influences colorectal cancer progression through both tumor-promoting bacterial signaling pathways and immune-modulating microbial metabolites. Fusobacterium nucleatum enhances CRC growth through Annexin A1-mediated amplification of Wnt/β-catenin signaling, while beneficial SCFAs strengthen anti-tumor immunity. Conversely, harmful microbiota-modified bile acids suppress CD T-cell function and promote tumor progression. These findings suggest that microbiome-based prevention strategies may require both enhancement of protective microbial metabolites and limitation of harmful bacterial signaling pathways. Further mechanistic research may help identify targeted interventions capable of reducing colorectal cancer risk through modulation of the gut microbiome.

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