The World Health Organization declared three years ago that circumcision should
be part of any strategy to prevent HIV infection in men. The organization based
its recommendation on three randomized clinical trials in Africa that found the
incidence of HIV was 60 percent lower in men who were circumcised. Although this
“research evidence is compelling,” wrote the WHO panel assigned to the topic,
there was little evidence explaining how circumcision might reduce a man’s risk
of acquiring HIV.
Now comes an answer in a new study, published in the January 6 issue of PLoS
ONE, which found that there are gross changes in the penis’s microbiome
following circumcision, suggesting that shifts in the bacterial environment
could account, in part, for the differences in HIV infection. Families of
anaerobic bacteria, which are unable to grow in the presence of oxygen, are
abundant before circumcision but nearly disappear after the procedure. The
researchers suspect that in uncircumcised men, these bacteria may provoke
inflammation in the genitalia, thereby improving the chances that immune cells
will be in the vicinity for HIV viruses to infect.
“We never knew that there were that many anaerobic bacteria on the uncircumcised
penis before [this study],” says Ronald Gray, a reproductive epidemiologist at
Johns Hopkins Bloomberg School of Public Health and one of the lead authors on
the current study. According to a 2006 survey, 56.1 percent of boys in the U.S.
are circumcised. In its recommendation, the WHO panel stated that circumcision
efforts would be most beneficial in parts of the world where less than 20
percent of boys are circumcised.
Gray, who is also working with one of the three randomized clinical trials on
which WHO based its recommendation, adds that, “If we can show that these
anaerobic bacteria are associated with HIV, then one could develop
microbicides?antiseptics or targeted antibiotics ?that might provide
protection.”
In the current study Gray and his colleagues compared the microbiota of 12
HIV-negative Ugandan men ages 15 to 49 before and after they were circumcised.
It was important to limit the study to HIV-negative participants because
infection itself can throw off the bacterial environment of the penis, says
Lance Price, a research director at the Translational Genomics Research
Institute in Flagstaff, Ariz., and co-author on the study. The team collected
swabs from an area between the head and shaft of the men’s penises before and
one year after circumcision. Then the researchers performed polymerase chain
reaction analysis of a gene that is shared by, although not identical in,
numerous bacterial families. The analysis allowed for identification of
different bacterial families as well as abundance counts.
At 12 months after circumcision, the microbiome’s predominant bacterial
population had shifted from anaerobic to aerobic, which require oxygen to grow.
Whereas the researchers detected similar number of bacteria belonging to aerobic
families in circumcised and uncircumcised samples, they found that the abundance
of anaerobic family members plummeted after circumcision. As the authors wrote,
this decrease makes sense because there is an oxygen-deprived area under the
foreskin that is lost after circumcision.