Circumcision reduces the amount of mucosal tissue exposed to vaginal secretions during heterosexual intercourse and thus may reduce the potential interactions between the virus and its target immune cells.Circumcision results in a process called keratinization, whereby the top layer of the inner foreskin becomes thicker, which may provide additional protection for the underlying target immune cells.Circumcision-associated physiological changes of the penis - including lower moisture and oxygen availability around the head of the penis - may reduce the number of pro-inflammatory anaerobic bacteria that could make the target immune cells more vulnerable to HIV infection.
"These potential explanations are not mutually exclusive and may work in concert to reduce HIV risk," said Dr. Price, an Associate Investigator in TGen's Pathogen Genomics Division.
The new study found that specific bacteria taxonomically defined as anaerobic dominated the microbiota of the penile coronal sulcus before circumcision. However, after circumcision, these bacteria decreased dramatically.
"Thus, the reduction in the putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases," the study concluded.
Bacteria that form in the absence of, or lower levels of, oxygen may be associated with inflammation and the activation of Langerhans cells. These cells, which are part of the body's normal immune system, work to capture and degrade the virus when they are in an inactivated state. But once activated, the Langerhans cells become re-directed to assisting HIV infection by presenting the virus to CD4+ cells.
Circumcision remains a controversial procedure that has ardent proponents and opponents. Those who favor circumcision point to many studies demonstrating lower risk for sexually transmitted diseases associated with circumcision. Those who oppose circumcision point to the potential dangers of the procedure itself as well as cultural concerns.
This new study shows that circumcision significantly changed the penile bacterial ecology.
"The concept that there are good and harmful bacteria is essential to studying the human microbiome. Our work showed that the profile of the penile bacterial communities changed significantly after circumcision," said Dr. Cindy M. Liu, a medical doctor and researcher at both TGen and Northern Arizona University. She is the paper's other co-lead author.
"With the decrease in putative anaerobic bacteria, we saw a correlated increase in the proportion of other specific facultative anaerobic and aerobic bacteria. This suggests that eliminating harmful bacteria may be only half of the needed action. Ensuring that the niche left by pre-circumcision anaerobic bacteria are filled with "good" bacteria will also be critical," Dr. Liu said.
TGen and Johns Hopkins researchers plan to conduct more studies to determine whether specific bacteria are associated with increased HIV risk and if such bacteria can be eliminated using non-surgical strategies.
Source: The Translational Genomics Research Institute