Targeting cancer hallmarks with microbiome-derived bacteriocins and postbiotics: molecular mechanisms and...

The human microbiome is an abundant reservoir of bioactive molecules with considerable therapeutic potential in oncology. Among these microbial products, bacteriocins and other postbiotic metabolites have emerged as promising anticancer agents due to their diverse biological activities and ability to modulate multiple cancer-related pathways. Growing evidence suggests that microbiome-derived compounds may provide novel opportunities for the development of safer and more targeted cancer therapeutics.

This review aims to comprehensively evaluate the current knowledge on bacteriocins and postbiotic metabolites as anticancer agents, highlighting their sources, structural and functional properties, mechanisms of action, computational-assisted discovery approaches, nanotechnology-based delivery systems, and challenges associated with clinical translation.

A critical analysis of the available literature was conducted to summarize the biological characteristics of bacteriocin-producing microorganisms, the classification and mechanisms of bacteriocins, and the anticancer activities of major postbiotic metabolites. Recent advances in molecular docking, molecular dynamics simulations, systems biology, artificial intelligence, and nanotechnology-based drug delivery platforms were also examined to assess their contributions to therapeutic development.

Bacteriocins exhibit anticancer effects through multiple mechanisms, including disruption of cancer cell membranes, induction of apoptosis, regulation of oxidative stress, inhibition of cell proliferation, suppression of angiogenesis and metastasis, epigenetic modulation, and enhancement of antitumor immune responses. In addition, postbiotic metabolites such as short-chain fatty acids, indole derivatives, reuterin, and microbial exopolysaccharides contribute to tumour suppression and modulation of host-microbe interactions. Computational approaches have accelerated the identification and optimization of bacteriocin-derived therapeutic candidates, while nanotechnology-based delivery systems have improved their stability, bioavailability, and tumour-targeting capabilities. Nevertheless, challenges including limited clinical evidence, non-standardized experimental methodologies, poor pharmacokinetic properties, manufacturing constraints, and regulatory barriers remain significant obstacles to clinical implementation.

Bacteriocins and postbiotic metabolites represent a versatile and promising class of microbiome-derived anticancer agents with substantial potential for precision oncology. The integration of microbiome science, synthetic biology, computational drug discovery, and advanced drug delivery technologies is expected to facilitate the translation of these natural compounds into clinically effective cancer therapeutics. Future research should focus on mechanistic validation, large-scale production, pharmacological optimization, and well-designed clinical studies to accelerate their development and therapeutic application.