The penile microbiota of Black South African men: relationship with human papillomavirus and HIV infection

Abstract

Background: To date, the microbiota of the human penis has been studied mostly in connection with circumcision, HIV risk and female partner bacterial vaginosis (BV). These studies have shown that male circumcision reduces penile anaerobic bacteria, that greater abundance of penile anaerobic bacteria is correlated with increased cytokine levels and greater risk of HIV infection, and that the penile microbiota is an important harbour for BVassociated bacteria. While circumcision has been shown to significantly reduce the risk of acquiring human papillomavirus (HPV) infection, the relationship of the penile microbiota with HPV is still unknown. In this study, we examined the penile microbiota of HPV-infected men as well as the impact of HIV status. Results:The penile skin microbiota of 238 men from Cape Town (South Africa) were profiled using Illumina sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Corynebacterium and Prevotella were found to be the most abundant genera. Six distinct community state types (CSTs) were identified. CST-1, dominated by Corynebacterium, corresponded to less infections with high-risk HPV (HR-HPV) relative to CSTs 2-6. Men in CST-5 had greater relative abundances of Prevotella, Clostridiales, and Porphyromonas and a lower relative abundance of Corynebacterium. Moreover, they were significantly more likely to have HPV or HR-HPV infections than men in CST-1. Using a machine learning approach, we identified greater relative abundances of the anaerobic BV-associated bacteria (Prevotella, Peptinophilus, and Dialister) and lower relative abundance of Corynebacterium in HR-HPV-infected men compared to HR-HPV-uninfected men. No association was observed between HIV and CST, although the penile microbiota of HIV-infected men had greater relative abundances of Staphylococcus compared to HIVuninfected men.(Continued on next page) Conclusions: We found significant differences in the penile microbiota composition of men with and without HPV and HIV infections. HIV and HR-HPV infections were strongly associated with greater relative abundances of Staphylococcus and BV-associated bacterial taxa (notably Prevotella, Peptinophilus and Dialister), respectively. It is possible that these taxa could increase susceptibility to HIV and HR-HPV acquisition, in addition to creating conditions in which infections persist. Further longitudinal studies are required to establish causal relationships and to determine the extent of the effect.

The Penile Microbiota in Uncircumcised and Circumcised Men: Relationships With HIV and Human Papillomavirus Infections and Cervicovaginal Microbiota

“…This hypothesis is based on the observation that HIV reduces semen microbiota diversity, which is restored after long-term ART, possibly through immune reconstitution (86). We further observed that among the bacterial taxa that were differentially abundant between men with and without HIV infection (e.g., Staphylococcus, Strenotrophominas, Propionibacterium, and Nosocomiicoccus), it was only an unclassified bacterium in the order Actinomycetales that was associated with HIV infection after adjustment for multiple comparisons (53). The association between HIV infection and the relative abundances of certain penile bacteria could mean that such bacteria either increase the risk of HIV infection or occur as a consequence of HIV infection.…”

“…We used a machine learning approach to identify the bacterial taxa that were differentially abundant in men with vs. without HPV and HR-HPV infections. We noted that higher relative abundances of BV-associated bacteria (Prevotella, Peptinophilus, and Dialister) and lower relative abundance of Corynebacterium were distinctively associated with HR-HPV infections (53). It seems, therefore, that there might be a link between Corynebacterium and protection against penile HPV infection.…”

“…In this study, 54.6 and 42.9% of the men were positive for HPV and HR-HPV infections, respectively, (53). Men with Corynebacteriumdominated penile microbiota were less likely to have HR-HPV compared to men with pooled non-Corynebacteriumdominated penile microbiota, including the ones dominated with BV-associated bacteria or Lactobacillus (53). Men with diverse penile microbiota, specifically dominated by Prevotella, Clostridiales, and Porphyromonas and a lower relative abundance of Corynebacterium were more likely to have HPV or HR-HPV infections than men with Corynebacterium-dominated penile microbiota (53).…”

“…On the other hand, traditional male circumcision (TMC) is usually performed by a medically untrained provider in a non-clinical setting, with either the foreskin partially or fully (completely) removed (46-50) using different cutting techniques (51). TMC is common in many settings within sub-Saharan Africa (45)(46)(47)(48)(49)(50)(51)(52)(53), and is performed as a ritual to initiate the males into manhood (46,49).…”

“…Studies that have examined penile microbiota using cohorts of uncircumcised and circumcised men (25,41,53,(70)(71)(72)(73) found notable differences in the penile microbiota of these two groups of men-observations that overlap with those of longitudinal studies (40,57). For instance, higher relative abundances of Porphyromonas (6.4 vs. 0.3%) and Prevotella (12.9 vs. 0%) and lower relative abundance of Staphylococcus (5.5 vs. 26.6%) were found in the coronal sulci of 5 uncircumcised adolescent men compared to 12 circumcised adolescent men (73).…”