Rupert Kaul

Problem HIV susceptibility is linked to the penile immune milieu (particularly IL‐8 levels) and microbiome. The effects of insertive vaginal sex itself on penile immunology and microbiota are not well described. Method of study We compared the immune milieu and microbiology of the coronal sulcus (CS) and distal urethra in 47 uncircumcised Ugandan men reporting ever ( n = 42) or never ( n = 5) having had vaginal intercourse. Soluble immune factors were assayed by multiplex ELISA, and penile bacteria abundance by 16S rRNA qPCR and sequencing. Co‐primary endpoints were penile levels of IL‐8 and soluble E‐cadherin. Results Independent of classical STIs, men reporting prior vaginal sex demonstrated elevated IL‐8 levels in both the coronal sulcus (1.78 vs. 0.81 log10 pg/mL, p = .021) and urethra (2.93 vs. 2.30 log10 pg/mL; p = .003), with a strong inverse relationship between urethral IL‐8 levels and the time from last vaginal sex ( r = –0.436; p = .004). Vaginal sex was also associated with elevated penile IL‐1α/β and soluble E‐cadherin (sEcad), a marker of epithelial disruption. Gardnerella vaginalis ( Gv ) was only present in the penile microbiome of men reporting prior vaginal sex, and urethral Gv absolute abundance was strongly associated with urethral inflammation ( r = 0.556; p < .001); corynebacteria were enriched in the CS of men reporting no prior vaginal sex and were associated with reduced CS inflammation. Conclusions Sexual intercourse was associated with sustained changes in penile immunology, potentially mediated through microbial alterations, in particular the urethral abundance of G. vaginalis . Future studies should further characterize the effects of sexual debut on penile bacteria and immunology.