Navigating the Gut–Prostate Axis: The Gut Microbiome in Prostate Cancer Resistance and Targeted Interventions

Abstract

In recent years, the gut microbiome has been increasingly recognized as an important factor in regulating treatment responses and disease progression in prostate cancer (PCa). We synthesized literature published over the past five years, focusing on preclinical and clinical studies linking the microbiome to PCa treatment outcomes. There is accumulating evidence that gut microbiota dysbiosis and its associated metabolites can modulate key biological processes, such as androgen metabolism, inflammatory signaling pathways, and antitumor immune responses. These processes affect the sensitivity of PCa patients to androgen deprivation therapy (ADT) and other systemic treatments. The available evidence suggests that the gut microbiome has the potential to serve as a predictive biomarker for treatment response and could represent a novel target for interventional precision therapy in PCa. This narrative review summarizes the latest research on the “gut–prostate axis”, focusing on the role of the gut microbiome in regulating therapeutic responses in PCa and the underlying mechanisms. Finally, we address current limitations, including the predominance of preclinical evidence, methodological heterogeneity, and the critical need for longitudinal clinical validation to distinguish causality from association.