Integrating probiotics and microbiome-derived metabolites into cancer therapy: mechanistic insights, multi-omics strategies, and clinical potential

• Probiotics, mainly Lactobacillus and Bifidobacterium , generate bioactive metabolites with antimicrobial and anticancer functions. • Their mechanisms include modulation of gut microbiota, inhibition of pathogens, receptor competition, and regulation of gene expression. • Probiotics influence carcinogenesis by suppressing tumor growth, promoting apoptosis, and modulating immune responses, with potential to enhance chemo- and radiotherapy efficacy. • Clinical and preclinical evidence indicates therapeutic benefits in colorectal, breast, lung, cervical cancers, and leukemia. Probiotics and their microbiome-derived metabolites are increasingly recognized as key players in cancer biology, functioning not only as regulators of gut homeostasis but also as modulators of tumor development, therapeutic response, and treatment-associated toxicities. These beneficial microorganisms exert their effects through diverse mechanisms, including microbiota remodeling, pathogen suppression, immune reprogramming, epigenetic regulation, and production of bioactive metabolites such as short-chain fatty acids, bacteriocins, vitamins, and exopolysaccharides. These metabolites influence fundamental processes of tumorigenesis by inducing apoptosis, inhibiting proliferation, modulating angiogenesis, and reshaping the tumor microenvironment toward a more immunoresponsive phenotype. Importantly, probiotics have been shown to enhance the efficacy of immune checkpoint inhibitors, mitigate chemotherapy- and radiotherapy-induced gastrointestinal complications, and detoxify carcinogens, thereby acting as supportive adjuncts in oncology. Emerging computational biology and multi-omics approaches—including genomics, metabolomics, and transcriptomics—have accelerated the identification of biosynthetic gene clusters and metabolic pathways responsible for anticancer bioactivity, allowing mechanistic mapping of probiotic–host–tumor interactions. Integration of these datasets highlights the potential for precision-guided probiotic formulations and engineered microbial consortia as novel therapeutic platforms. Nevertheless, clinical translation is hindered by strain-specific variability, host microbiome heterogeneity, lack of standardized protocols, and limited large-scale randomized trials. Addressing these gaps through harmonized methodologies, deeper mechanistic validation, and patient-tailored microbiome profiling will be essential for transforming probiotics from supportive dietary supplements into precision-based oncology therapeutics. This review integrates mechanistic insights, multi-omics strategies, and clinical evidence on probiotics and their metabolites in cancer therapy. By converging advances in microbial biotechnology, systems biology, and translational oncology, we propose probiotics as sustainable and precision-driven agents capable of reshaping the landscape of cancer prevention and treatment