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

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.