Gut microbiota-metabolism axis in digestive tumors: Emerging targets for novel therapies (Review).

Abstract

Digestive tumors, including malignancies associated with the gastrointestinal tract, represent a notable global health burden. Advances in microbiome research have highlighted that the gut microbiota-metabolism axis and its associated metabolic derivatives are key modulators of tumorigenesis, immune evasion and treatment responses. The present review aimed to comprehensively discuss how key microbial metabolites, such as polyamines, short-chain fatty acids, bile acids and other compounds reshape the tumor microenvironment, modulate cellular signaling and affect immune responses. By integrating insights from microbiology, immunology, oncology and metabolic changes in digestive tumors, evidence suggests that the microbiota contributes to cancer progression through mechanisms involving epigenetic regulation, metabolic reprogramming, genotoxicity and production of inflammatory mediators. Beneficial bacteria, such as Akkermansia muciniphila and Faecalibacterium prausnitzii, exhibit antitumor activity, whereas pathogenic species, such as Helicobacter pylori and Fusobacterium nucleatum, are associated with oncogenic properties. Based on a literature search, microbiota-targeted therapy seems to be promising for the management of pathological conditions, especially digestive diseases. Further investigations into the pharmaceutical application of microbiota through prebiotics, probiotics and metabolite-targeted interventions, along with multi-omics integration and microbiome-host interactome validation, would be promising for improving personalized medicine and precision oncology.