Penis Microbiome Could Enhance Risk of Infection with HIV

New research explores how the bacteria on the penis can leave men more susceptible to infection with HIV.

Since 1981, the HIV/AIDS pandemic has infected more than 70 million people, killing almost 40 million. As research on a vaccine and treatments move forward, other studies focus on reducing transmission of the virus. In a study published in mBio, scientists from the Milken Institute of Public Health at the George Washington University, reveal that penile bacteria could be a risk factor for HIV.

We already know that HIV has little fear of the human immune system. According to study authors, two factors needed for human infection with HIV include the virus itself and activation of immune CD4 cells in the mucous membranes at its viral point of entry. The demographics of the bacteria living on the penis, specifically under the foreskin, may be helping the virus gain entry into the body of uncircumcised males.

A Study of the Penile Microbiome

The study of the composition of the microbiome, or community of microbes, which live on and in the human body seems to gain significance each day. The bacteria on the skin can crowd out deadly skin pathogens, while a healthy gut microbiome helps us digest our food and possibly even avoid autoimmune diseases.

The study of these communities naturally extends to the penis, and in this case, the information gained could help researchers and individuals know more about how to avoid infection with HIV.

According to this study, the foreskin is the primary point of viral entry and exposure in uncircumcised heterosexual men. If the population of genital bacteria that reside under the foreskin promotes inflammation — which could put a man at greater risk of acquiring HIV if exposed. How does that work?

The study authors point out that inflammation is a response by the immune system that increases populations of CD4 T cells in the foreskin. HIV targets these cells when trying to gain entry into the body. More CD4 cells at the gateway mean there are more pathways into the body.

So where does the inflammation come from? When the balance of the penile microbiome is perturbed, it enters "dysbiosis." Dysbiosis means a little bit like how it sounds — a dysfunction of the biome, or according to the study, "an imbalance in the microbiome that compromises health." Inflammation — in the vaginal microbiome or the penile microbiome — reduces natural defenses to infection with HIV. This study suggests that this imbalance, and its resulting inflammation, could be caused by "penile anaerobes."

Penis Microbiome Could Enhance Risk of Infection with HIV — Anaerobic bacteria, including the bacterium Prevotella. *Image by Jim Pledger and Dr. V.R. Dowell, Jr./CDC*

Here is another term that sounds a bit like it is — anaerobes are organisms that do not need oxygen for growth. Anaerobes on the penis reside mostly under the foreskin of an uncircumcised male, and this study took a look at how that might impact infection rates. More anaerobic bacteria of questionable character mean more inflammation, which makes for more fertile ground for infection by HIV.

Between 2004 and 2006, the research team monitored uncircumcised men in Rakai, Uganda between 15 to 49 years of age. At six, 12 and 24-months into the monitoring, swabs of penile bacteria were collected, stored, and DNA analyzed. The results were pretty straightforward:

Of 182 uncircumcised men in the study, 46 men became infected with HIV during the study period.
Men who contracted HIV had much higher numbers of penile anaerobes including Prevotella, Dialister, Mobiluncus, and Peptostreptococcus.
Study authors looked specifically at which types of bacteria were significantly reduced after male circumcision. For an uncircumcised man, these bacteria composed 62% of the total bacterial load living under their foreskin. Men who acquired HIV during the study period had higher levels of these penile anaerobes. As noted in the study, "response of the immune system to shifts in the penile microbiome may facilitate productive infection by HIV."
Researchers also found that inconsistent use of condoms and nonmarital sexual relations increased the risk of acquiring HIV. The danger is amplified as unprotected sex shares these anaerobic bacteria among partners.
In this study, the authors note that genital washing was not effective in reducing transmission of HIV, but that other solutions, including narrow-spectrum antimicrobials, could be of help to reduce risk from penile anaerobes. Circumcision was shown to "largely resolve" the issue of anaerobes in the microbiome but doesn't completely reduce risk.

This study offers evidence that bacteria under the foreskin may create an additional risk factor for acquiring HIV or other sexually transmitted diseases for uncircumcised men, and their partners. As noted fairly plainly by the first author on the paper in a press release, Cindy Liu: "This study is the first to suggest that the bacteria colonizing the penis can be an independent risk factor for HIV in men."