Abstract
Introduction The interplay between the genital microbiome and the host immune system may modify one’s susceptibility to sexually transmitted infections. We examined the impact of circumcision on the penile microbiome and how it affects local immune response and potentially modifies the host’s risk for HIV. Methods Using real-time PCR, DNA sequencing, and Luminex multiplex assays, we studied the penile microbiome and levels of pro-inflammatory cytokines in the coronal sulcus of adult men who were randomized to immediate or delayed male circumcision in Rakai, Uganda. Results Uncircumcised men frequently had high abundances of anaerobic bacteria, including Prevotella , Porphyromonas , and species of Clostridiales Family XI. Penile anaerobes decreased after male circumcision, replaced by low abundances of skin-associated bacteria such as Staphylococcus and Corynebacterium . Among the pro-inflammatory cytokines measured, the level of IL-8 correlated significantly with penile anaerobe abundance, which remained persistently elevated in uncircumcised men but decreased after circumcised men. Discussion Our findings suggest that the penile microbiome may play a role in host susceptibility to HIV. Circumcision significantly decreased penile anaerobes and local production of pro-inflammatory cytokines, which may reduce HIV target cells recruitment and activation in the penile epithelium.
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