Pathological phimosis is associated with foreskin immune cell infiltration but not microbiota composition

The penile microbiota has been implicated in genital inflammation and increased risk of HIV, HPV, HSV-2, and female-partner bacterial vaginosis in adult males, yet its development during childhood and potential role in pediatric foreskin pathologies remain unknown. We characterized the coronal sulcus microbiota of 75 pediatric males (median age 8.5 years; 43% with pathological phimosis) before and after circumcision and compared these profiles to 56 uncircumcised adult men. Pediatric penile microbiota were highly diverse, dominated by strict and facultative anaerobes, and loosely structured compared to adults, who exhibited two distinct, ecologically organized communities. Circumcision markedly reduced anaerobic taxa and increased Corynebacterium and Staphylococcus. Pathological phimosis (the inability to retract the foreskin due to scarring) was associated with increased densities of CD3+ T cells, CD4+ cells, and CD11c+ dendritic cells, suggesting an adaptive immune mechanism; however, pathological phimosis was not associated with microbiota composition. Nonetheless, Mobiluncus was negatively correlated with CD11c+ dendritic cells, while Campylobacter and Peptoniphilus were negatively correlated with CD56+ NK cells, suggesting microbe-immune interactions. Our data suggest pathologic phimosis is driven by adaptive immune responses but not by specific bacteria; the pathology may be driven by differences in host responses to bacteria or by other stimuli, such as fungal antigens. Our data also demonstrate that the transition to adulthood is accompanied by reorganization of penile communities into structured types previously linked to infection risk, highlighting puberty as a potential window for interventions that promote protective adult microbiota and improve lifelong sexual and reproductive health.

The human penis hosts complex bacterial communities that can influence inflammation, infection risk, and sexual health, but little is known about how these communities form early in life or whether they contribute to childhood foreskin inflammatory disorders. We combined 16S rRNA sequencing with quantitative microscopy to investigate the penile microbiota in boys and its relationship to pathological phimosis, a common condition marked by foreskin scarring. We found that phimosis is associated with infiltration of T cells and dendritic cells, indicating an adaptive immune process, but with no associations with specific bacteria. We also show that penile microbiota reorganize during puberty into structured community types previously linked to HIV and sexually transmitted infection risk. These findings suggest that childhood pathologic phimosis is mediated by adaptive immune responses rather than driven by specific bacterial communities and identify puberty as a critical period for shaping adult penile microbiota, with implications for lifelong genital health.