Changes in bacteria within the penis microbiome documented for
the first time
PHOENIX, Ariz. -- Jan. 5, 2010 -- Circumcision, which
substantially lowers HIV risk in men, also dramatically changes the
bacterial communities of the penis, according to a study led by
scientists at the Translational Genomics Research Institute (TGen)
and Johns Hopkins University and published Jan. 6 in the scientific
journal PLoS ONE.
And these bacterial changes may also be associated with earlier
observations that women whose male partners are circumcised are
less likely to develop bacterial vaginosis, an imbalance between
good and harmful bacteria.
The study - The Effects of Circumcision on the Penis Microbiome -
could lead to new non-surgical HIV preventative strategies for the
estimated 70 percent of men worldwide (more than 2 billion) who,
because of religious or cultural beliefs, or logistic or financial
barriers, are not likely to become circumcised.
"It has important public-health ramifications," said Dr. Lance B.
Price, Director of TGen's Center for Microbiomics and Human Health
and co-lead author of the scientific paper, which describes the
world's first molecular assessment of the bacterial diversity of
the male reproductive organ.
This new study is part of a larger effort by the U.S. National
Institutes of Health to study and describe the "human microbiome" -
the microbes that exist collectively on and in the human body.
Other projects are focused on microbiomes involving the skin, nose,
mouth, digestive and female genitourinary tract. Jointly, the goal
of these projects is to define the various roles of microbes in
human health and disease.
In investigating the impact of male circumcision on the penis
microbiome, a collaborative team from TGen and the Johns Hopkins
Bloomberg School of Public Health found for the first time that
circumcision significantly changes the bacterial community of the
penis.
*
Other epidemiological studies have shown that male circumcision is
associated with significant reductions in HIV acquisition in
men.
The strongest evidence for a cause-and-effect relationship between
circumcision and HIV risk reduction came from three
randomized-control trials in sub-Saharan Africa, where the
circumcision rate is relatively low and the HIV infection rate is
relatively high. All three demonstrated a more than 40 percent
reduction in HIV acquisition among circumcised men.
The largest of these three studies - in Rakai, Uganda - was led by
Dr. Ronald H. Gray, a renowned epidemiologist at Johns Hopkins and
the scientific paper's senior author. Dr. Gray's group collected
penile swabs from all of the circumcision trial study participants,
which provided the data for the new TGen-Johns Hopkins study.
The new study found that circumcision - the removal of the
foreskin, or prepuce, from the penis - eliminates an area of mucous
membrane and dramatically changes the penile bacterial ecosystem.
Significantly, TGen's analysis of more than 40 types of bacteria,
using a 16S rRNA gene-based pyrosequencing approach, suggests that
the introduction of more oxygen following circumcision decreases
the presence of anaerobic (non-oxygen) bacteria and increases the
amount of aerobic (oxygen-required) bacteria.
"This study clearly shows that male circumcision markedly reduces
genital colonization with anaerobic bacteria in men,'' said Dr.
Gray, the William G. Robertson Jr. Professor in Population and
Family Planning at the Johns Hopkins Bloomberg School of Public
Health.
"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. Our randomized trials have shown that
male circumcision prevents HIV infection in men and protects their
female partners from vaginal infections, especially bacterial
vaginosis. It is possible that the virtual elimination of anaerobic
bacteria by circumcision contributes to these benefits of the
procedure," Dr. Gray said.
*
Several mechanisms have been proposed for how circumcision reduces
HIV acquisition in men:
-- 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.
*
Also involved in the study published today were: the University of
Maryland School of Medicine; and Makerere University's School of
Public Health, Kampala, Uganda.
# # #
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
*
About Johns Hopkins
As a leading international authority on public health, the Johns
Hopkins Bloomberg School of Public Health is dedicated to
protecting health and saving lives. Every day, the School works to
keep millions safe from illness and injury by pioneering new
research, deploying its knowledge and expertise in the field, and
educating tomorrow's scientists and practitioners in the global
defense of human life. For more information, visit:
www.jhsph.edu.