The Effects of Circumcision on the Penis Microbiome

Lance B Price,Maria J Wawer,Jolene Bowers,Cindy M Liu,Jacques Ravel,Ronald H Gray,Matthew K Lau,Maliha Aziz,Paul S Keim,Kristine E Johnson,David Serwadda,Stefan Bereswill

doi:10.1371/journal.pone.0008422

Abstract

BackgroundCircumcision is associated with significant reductions in HIV, HSV-2 and HPV infections among men and significant reductions in bacterial vaginosis among their female partners.Methodology/Principal FindingsWe assessed the penile (coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3–V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significant decrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families—Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)—were uniquely abundant before circumcision. Within these families we identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp. Conclusions/SignificanceThe anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.

Highlights

Randomized trials have shown that male circumcision decreased risk of HIV, HSV-2, and HPV infections in men [1,2,3,4]
While immature DC-SIGN+ dendritic cells are capable of mediating HIV-1 trans-infection of the CD4+ T-cells [12], Langerhans’ cells could play a dual role depending on their activation state
We found a total of 42 unique bacterial families in the coronal sulci microbiota, with 38 bacterial families among pre-circumcision samples versus 36 detected among post-circumcision samples (Table 1)

Summary

Introduction

Randomized trials have shown that male circumcision decreased risk of HIV, HSV-2, and HPV infections in men [1,2,3,4]. One these trials demonstrated decreased risk of trichomoniasis and bacterial vaginosis (BV) in the female sexual partners of circumcised men [5] as well as decreased symptomatic genital ulceration in both men and their female sexual partners [4,6]. It is important to better understand the biological mechanisms by which male circumcision reduces the risk of HIV infection as this may lead to the development of novel, non-surgical prevention strategies. Circumcision is associated with significant reductions in HIV, HSV-2 and HPV infections among men and significant reductions in bacterial vaginosis among their female partners

Methods

Results

Conclusion