The Gut–Prostate Axis: Mechanistic Insights and Nanotechnology Driven Therapeutic Strategies

ABSTRACT

Prostate cancer (PCa) remains a leading cause of oncological morbidity and mortality globally, presenting a critical public health challenge that escalates with rapidly aging demographics. While traditional research has primarily focused on intraprostatic genetic aberrations and localized androgen receptor (AR) signaling, an emerging paradigm shift highlights the profound influence of the systemic macroenvironment, specifically mediated through the “Gut–Prostate Axis”. This bidirectional communication network links gastrointestinal dysbiosis to prostate malignancy through complex mechanisms, including microbial steroid hormone biosynthesis, compromised intestinal barrier integrity, chronic systemic inflammation, and the systemic circulation of bioactive microbial metabolites. Despite the compelling therapeutic potential of targeting this axis, conventional microbial interventions, such as raw biotherapeutics, lifestyle modifications, and fecal microbiota transplantation (FMT), are heavily restricted by poor gastrointestinal stability, lack of anatomical target specificity, and variable clinical reproducibility. To bridge this translational gap, the “Microbiome‐Nanotech” interface has emerged as a revolutionary frontier. By leveraging smart, stimuli‐responsive nanomaterials, nanotechnology offers sophisticated platforms capable of protecting fragile postbiotics for site‐specific colonic release or systemically delivering targeted therapeutics directly to the neoplastic prostate microenvironment. This review provides a comprehensive analysis of the multilayered molecular and immunological pathways that govern the gut–prostate axis, while critically evaluating state‐of‐the‐art nanomedicine strategies to translate these microbial insights into precise, clinically viable therapeutic interventions for advanced PCa.