The Gut-Prostate Axis: Decoding the Interplay of Environmental Factors, Microbial Metabolites, and Hormonal Regulation in Prostate Cancer Pathogenesis

Prostate cancer remains one of the most common malignancies in men, with its progression strongly influenced by androgen signaling. While genetic alterations are well-documented in prostate cancer, growing evidence highlights the contribution of environmental factors, particularly diet and the gut microbiome, in modulating disease risk and therapy response. The gut microbiota plays a crucial role in regulating host metabolism, immune responses, and hormone activity. Recent findings suggest that specific microbial communities influence androgen biosynthesis and metabolism through enzymes such as β-glucuronidase, altering systemic androgen availability and imp acting tumor progression. Additionally, microbial metabolites, including short-chain fatty acids, secondary bile acids, and bacterial genotoxins, can affect inflammatory pathways and cellular signaling relevant to prostate tumorigenesis. Experimental studies also indicate that modifying the gut microbiota through dietary interventions, probiotics, or fecal microbiota transplantation can influence tumor growth and improve responses to immunotherapy and hormone-based treatments. In this review we present the current knowledge on gut-prostate axis, examine the mechanistic links between microbial activity and prostate cancer biology, and discuss emerging microbiome-based strategies as potential therapies. A deeper understanding of this bidirectional crosstalk could pave the way for microbiome-informed approaches to prevention, diagnosis, and personalized treatment of prostate cancer.