Reprogramming Prostate Cancer Through the Microbiome

Jhommara Bautista¹Walter D Cardona Maya²Kelly Gancino¹Mishell Criollo¹Andrés López-Cortés^1*

• ¹Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
• ²Universidad de Antioquia, Medellín, Colombia

Prostate cancer (PCa) is a major global public health challenge, driven by a multifactorial interplay of genetic, epigenetic, hormonal and environmental determinants. In recent years, the human microbiome has emerged as a critical and previously underappreciated contributor to PCa initiation, progression, and therapeutic response. Emerging high-resolution multi-omics studies have demonstrated that microbial communities across the gut, urinary tract and prostate form a functional axis that shapes immune surveillance, hormonal metabolism, inflammatory tone and epigenetic regulation. Dysbiosis in these compartments promotes chronic inflammation, modulates androgen receptor signalling, and produces bioactive metabolites, including short-chain fatty acids, that activate oncogenic IGF-1/MAPK/PI3K and NF-κB/JAK/STAT pathways. Cross-compartmental trafficking of bacterial taxa and metabolites reinforces tumour-promoting circuits, while specific commensals such as Akkermansia muciniphila enhance antitumor immunity and improve responses to androgen deprivation therapy. Importantly, microbiota-derived factors also modulate microRNA (miRNAs) expression and epigenetic signatures, thereby affecting tumour plasticity and resistance to therapy. These mechanistic insights have catalysed interest in microbiome-based therapeutic approaches, including probiotics, prebiotics, faecal microbiota transplantation, dietary modulation and bacteriophage therapy, which hold promise for restoring eubiosis and enhancing treatment efficacy. Nevertheless, clinical translation remains limited by inter-individual variability and the need for well-designed, longitudinal studies integrating shotgun metagenomics, metabolomics and host-microbe interactomics. Overall, the prostate, urinary and gut microbiomes represent interconnected targets that may inform precision diagnostics and novel therapeutic strategies in PCa.