Circumcised vs. Uncircumcised; Differences in the Penile Microbiome

Introduction
The uncircumcised PMB
Post-circumcision PMB
Conclusions
References
Further reading


The human body is host to trillions of microbes. The penis also harbors its own microbiota, which changes with circumcision. This shift is associated with a significant lowering of the risk of several sexually transmitted infections (STIs).

Image Credit: Chinnapong/ShutterstockImage Credit: Chinnapong/Shutterstock

Circumcision refers to the removal of the foreskin, or prepuce, of the penis, leaving the glans exposed. This removes the moisture and anoxia of the space between the prepuce and the glans, which favors microbial growth.

Several trials have demonstrated the benefits of circumcision for both males and females. Among men, the risk of STIs like human immunodeficiency virus (HIV), herpes simplex virus 2 (HSV-2) and human papilloma virus (HPV), which can have deadly sequelae, is lowered after male circumcision.

In females too, the chances of trichomoniasis and bacterial vaginosis (BV) are reduced if the male partners are circumcised.

This has led to some health bodies recommending circumcision to reduce HIV transmission among men, even though this is not a universally acceptable or feasible measure for multiple reasons, economic, logistical, and cultural. Some researchers, therefore, are focused on teasing out the underlying protective mechanism, hoping thereby to replicate the protective effect without surgery.

The most likely pathway for the lower HIV risk in circumcised men appears to be the reduction of moisture and anerobic conditions on the glans, thus preventing the overgrowth of microbes that could cause inflammation. Inflammation promotes the entry of HIV by activating the langerin+ Langerhans' cells and DC-SIGN+ dendritic cells, both of which are HIV targets.

The former are supposed to destroy the virus and prevent the infection of T cells by HIV. However, when microbes induce the production of inflammatory molecules like lipopolysaccharide (LPS), Toll-like receptor (TLR), or tumor necrosis factor (TNF)-α, Langerhans cells are activated and become efficient hosts for the virus.

This occurs with bacteria like Staphylococcus aureus, Group B Streptococcus, and genital pathogens such as Candida albicans and Neisseria gonorrhea. It is important to understand the changes in the penile microbiome (PMB) following circumcision.

Image Credit: Volodimir Zozulinskyi/ShutterstockImage Credit: Volodimir Zozulinskyi/Shutterstock

The uncircumcised PMB

Prior to circumcision, there are over three dozen bacterial families in the PMB. About 40% are aerobic, but over a fifth are anerobic. Slightly more, nearly a quarter, are facultative anerobes. About a tenth are unclassified.

The most abundant microbes are from Clostridiales family XI and Prevotellaceae. Familywise, the most abundant include Pseudomonas, Janthinobacteria, Anaerococcus and other Clostridiales, Prevotella, and Staphylococcus. Gardnerella comprised most of the Bifidobacteriaceae, while Sneathia represented the majority of Fusobacteriaceae.

Other anerobes included several species of Dialister, Veillonella, Peptostreptococcus, and Porphyromonas. There were more dominant families before circumcision.

Post-circumcision PMB

After circumcision, there are significant changes in the composition of the PMB, both bacteria and fungi. Predominantly anerobic genera of bacteria show a marked decline, but those which mostly comprise facultative anerobes increase in abundance. These changes are often on the scale of hundreds of times the original value, turning the post-circumcision PMB into something closely resembling the healthy skin microbiome.

Corynebacteriaceae and Staphylococcaceae became abundant at this point, though they are less pronounced in pre-circumcision samples. Pseudomonaceae remained abundant before and after circumcision. While Corynebacteriaceae are aerobic, the others are facultative anerobes.

Clostridiales and Campylobacterales also registered a marked decline, along with the fungi Saccharomycetales and Pleosporales.

The relative abundance of Porphyromonas increased to over 6% from 0.3% in the uncircumcised, mirroring a rise in Bacteroidales; that of Prevotella to ~13% from zero, while that of Staphylococcus dropped from ~27% to ~6%. Both Prevotella and Staphylococcus are present at stable levels over time in the PMB.

Opportunistic pathogens such as Staphylococcus aureus and Enterococcus species as well as strains of E. coli, Pseudomonas aeruginosa, and Klebsiella, or Clostridia, are 2-3 times more likely to be found in uncircumcised men vs. circumcised.

Overall, the post-circumcision PMB lacked the heterogeneity associated with the uncircumcised samples. The PMB dominated by Pseudomonas species may be the dominant type, with variations depending on the environment, host genotype, and mucosal immunity.

Conclusions

Overall, the composition and diversity of penile microbiota is impacted by male circumcision.”

Prior to circumcision, the subpreputial space might harbor multiple anerobic bacteria that trigger inflammation under certain circumstances. This may cause a loss of integrity of the epithelial barrier.

Secondly, it could lead to the activation of Langerhans cells, present in abundance near the surface of the lightly keratinized skin of the inner aspect of the prepuce. These are the HIV target cells.

The result is the presentation of HIV by these cells to the CD4 follicular T cells within the lymph nodes draining that area. This could explain why the HIV risk, as well as that of other STIs, is lower in circumcised men.

Circumcision also causes a shift in the PMB because of the differences in the tolerances of the microbes to atmospheric oxygen. A greater proportion are made up of facultative anerobes but no significant change is observed in that of aerobic bacteria. Pseudomonadaceae and Oxalobacteraceae, which comprise the two most abundant phyla, showed a positive association with each other. However, they were negatively correlated with Clostridiales family XI, Prevotellaceae, Corynebacteriaceae, and Staphylococcaceae.

One set of authors concluded,

Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer.”

Image Credit: Design_Cells/ShutterstockImage Credit: Design_Cells/Shutterstock

References:

Further Reading

Last Updated: Mar 14, 2023

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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Comments

  1. Michael Glass Michael Glass Australia says:

    Ever since goodness knows when, people have been debating circumcision. If the foreskin was such a threat, how come countries that have widespread infant circumcision don't do better in life expectancy.

    Take Israel. Male life expectancy is high: 81.98 years, according to Worldometer. However, male life expectancy is even higher in Switzerland, Hong Kong, Iceland, Australia and Singapore. Switzerland, Hong Kong and Iceland generally don't circumcise their boys.

    What about infant death rates? The World Bank gives Israel an infant death rate of 3 per thousand. However, Monaco had 1 per thousand and countries that had a death rate of 2 per thousand included Estonia, Japan, Singapore, Slovenia, Finland, Norway, Sweden, Belarus, Luxembourg, Italy, Czechia and Cyprus. Portugal, Korea, Spain and Lithuania were also listed before Israel in the World Bank list.

    Regardless of any pathogens that may be lurking beneath the foreskin, that fact does not give Israel the lowest infant death rate in this data.

    • Bryan D. Garner Bryan D. Garner United States says:

      It reminds me of a parallel argument - Here in the US, most men are circumcised. Circumcision is supposed to reduce HIV. Yet the US has an above-average HIV infection rate. Guess it's true what they told me in sex ed - CONDOMS prevent diseases, not circumcisions.

  2. Bryan D. Garner Bryan D. Garner United States says:

    Do the microbes that live under the male foreskin also live under its analogue, the clitoral hood? If so, would removing the clitoral hoods of girls, as well as the foreskins of boys, double the chances of preventing HIV?

    If my foreskin is removed and I am HIV positive, do my female partner and I no longer need to worry about condoms? Will my circumcision make unprotected intervaginal ejaculation safe for her vis-a-vis contracting HIV from me?

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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