Cutibacterium acnes: An Emerging Prostate Cancer Pathogen

<i>Cutibacterium acnes</i> (<i>C. acnes</i>) has emerged as a potential contributor to prostate cancer (PCa) pathogenesis, yet the mechanistic basis remains unclear. This review explores the prevalence, persistence and mechanistic impact of <i>C. acnes</i> within the prostate to help decipher the functional consequence and diagnostic value of a <i>C. acnes</i> infection in this setting. We examine the evidence supporting <i>C. acnes</i> colonisation of both premalignant and malignant tissue, and critically evaluate how prostate tumour physiology, particularly hypoxia and low pH, may facilitate microbial persistence. Emerging data suggest that <i>C. acnes</i> modulates inflammatory and immune pathways, influencing macrophage activation, cytokine production, and the regulation of immune checkpoints. Additionally, we discuss studies demonstrating its involvement in DNA damage, host cell metabolism, and extracellular matrix remodelling. The identification of <i>C. acnes</i> in urinary and gut microbiomes, alongside the presence of its genomic DNA in extracellular vesicles in circulation indicate broad diagnostic potential. While discrepancies in methodology have hampered a consensus, recent genomic and functional studies provide new avenues to distinguish contamination from true pathogenicity. Ultimately, future research exploring whether <i>C. acnes</i> is a biomarker, bystander, or bona fide driver of PCa, and its potential role in personalised diagnostics are crucial to advance the field and unravel the predictive and therapeutic value of <i>C. acnes</i>. Clarifying this relationship will advance our understanding of microbiome-cancer dynamics and could help inform innovative early detection and screening strategies that improve patient care.