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Circumcision Alters Penis Microbiome; May Help Explain Past HIV Protection Studies

NEW YORK (GenomeWeb News) – Changes to the penis microbiome following circumcision may help protect against the transmission of HIV and other diseases, according to a paper appearing online today in PLoS ONE.

A team of researchers from the US and Uganda used 16S rRNA pyrosequencing to catalogue the microbes found on the penises of a dozen HIV-negative men from Africa before and after circumcision. Their findings suggest circumcision alters the penis microbiome — in particular, decreasing the representation of bacteria from anaerobic bacterial families, including those apparently involved in inflammatory processes.

Those involved say such changes may help explain the apparent circumcision-related decreases in the risk of HIV and other sexually transmitted diseases, such as herpes simplex virus or human papillomavirus, observed in past studies.

"This study clearly shows that male circumcision markedly reduces genital colonization with anaerobic bacteria in men," senior author Ronald Gray, an epidemiologist at Johns Hopkins University's Bloomberg School of Public Health, said in a statement. "These bacteria, which cannot grow in the presence of oxygen, have been implicated in inflammation and a number of infections affecting both men and women."

In 2001, Gray and his team reported in the Lancet that circumcision decreases HIV risk. And other studies support the notion that circumcision may not only decrease the risk of HIV in men but may also decrease the chance that their partners will get bacterial vaginosis infections. Several explanations have been proposed for this apparent protection. And now researchers have come up with another, suggesting microbial changes have a role in this process.

"Our randomized trials have shown that male circumcision prevents HIV infection in men and protects their female partners from vaginal infections, especially bacterial vaginosis," Gray said. "It is possible that the virtual elimination of anaerobic bacteria by circumcision contributes to these benefits of the procedure."

For the current study, Gray and colleagues used Roche 454 sequencing of V3-V4 hyper-variable 16S rRNA gene regions to assess the penis microbial communities from 12 Ugandan men before circumcision and up to a year after. All of the men included in the study were between the ages of 15 and 49 years old and were HIV-negative at the time of enrollment.

The team found 42 different bacterial families in the samples tested. But while some of these families were represented both before and after circumcision, such as bacteria from the Pseudomonadaceae family, others were specific to samples taken from uncircumcised or circumcised men.

For instance, prior to circumcision, the researchers reported, anaerobic bacteria belonging to the Clostridiales and Prevotellaceae families were commonly found in the penis microbiome. Among the representatives from these families: species implicated in past studies of bacterial vaginosis and microbes thought to promote inflammation of the genital mucosa.

In contrast, the levels of anaerobic bacteria decreased in samples taken after circumcision. The overall abundance and heterogeneity of penis-associated microbes also shifted after circumcision. The researchers detected bacteria from 38 families in the pre-circumcision samples, compared with 36 families in samples taken post-circumcision.

The new findings suggest the presence of more aerobic bacterial species and absence of some anaerobes may offer some protection against HIV and other sexually transmitted infections, though other factors — such as decreased mucosal tissue exposure to vaginal secretion and thickening of inner foreskin tissue — also seem to contribute.

"These potential explanations are not mutually exclusive and may work in concert to reduce HIV risk," co-lead author Lance Price, director of the Translational Genomics
Research Institute's Center for Metagenomics and Human Health, said in a statement.

The findings suggest it might eventually be possible to non-surgically decrease HIV risk in uncircumcised men — something the team reportedly plans to investigate in the future. For instance, strategies aimed at tweaking microbial communities could involve targeting suspect anaerobic microbes and/or bumping up the levels of beneficial microbes.

"[E]liminating harmful bacteria may be only half of the needed action," co-lead author Cindy Liu, a physician and researcher affiliated with TGen and Northern Arizona University, said in a statement. "Ensuring that the niche left by pre-circumcision anaerobic bacteria are filled with 'good' bacteria will also be critical."

The current study is part of a larger National Institutes of Health-led effort to understand the human microbiome. Researchers from other labs are currently investigating the microbial communities associated with the skin, nose, mouth, digestive, and female genitourinary tract.

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