Penile microbiomes have important implications for HIV susceptibility and broader reproductive health.

HIV remains a major global health issue, particularly in Sub-Saharan Africa, with treatment and prevention programs under increasing threat. Although pre-exposure prophylaxis (PrEP) is highly effective, barriers to uptake include stigma, cost and limited accessibility, highlighting the need for additional scalable prevention strategies. This review discusses the microbiomes of the male urethra and coronal sulcus, and their role in penile HIV acquisition. Key bacterial components of the coronal sulcus microbiome cause penile inflammation and enhance HIV susceptibility, and the latter is reduced after microbiome modification via penile circumcision or topical antibiotics. Similar to the coronal sulcus microbiome, the urethral microbiome is also shaped by sexual activity and also modulates local inflammation, although impacts on HIV susceptibility have not been defined. Importantly, the penile urethra may also serve as a reservoir for non-optimal vaginal bacteria, predisposing to bacterial vaginosis in female sexual partners. These insights highlight the potential of penile microbiome-targeted approaches to reduce HIV transmission and improve reproductive health.