Circumcision leads to changes in penis microbiome, study finds

The procedure is common in North America, West Africa, and the Middle East as a religious ritual or preventative health measure. In the U.S., about 64 percent of newborn boys undergo circumcision.

Circumcision and the penile microbiome

Researchers have known for a while that circumcision alters the penis microbiome. But they don't know exactly how the procedure affects human health. Now researchers are trying to fill in the gap.

"The hypothesis is that it has to do with the inflammation and bacteria under the foreskin," said Laura Bukavina, MD, MPH, a urologic oncology fellow at the Fox Chase Cancer Center in Philadelphia and senior author of the study.

For the study, investigators examined changes to the microbiome and mycobiome in 11 toilet-trained children who had undergone circumcision for cosmetic reasons or because of difficulty retracting their foreskin.

The researchers collected data using 16S ribosomal RNA sequencing to differentiate between enzymes and bacteria present on the foreskin. They found a significant shift in both the quantity and types of organisms present on the penis before and after circumcision, particularly those linked to penile inflammation in adulthood.

Results showed that certain types of bacteria, such as Clostridiales, Bacteroidales, and Campylobacterales, were found in lower quantities after circumcision. The bacteria have been implicated in several conditions, including inflammatory bowel disease, penile infections, and cancers.

While other bacteria species like Actinomycetales and Lactobacillales were found to be more abundant after circumcision. These bacteria have anti-inflammatory properties and are known to positively affect human health.

It is also worth mentioning that the organism typically responsible for urinary tract infections (UTIs), Escherichia coli, was not found in either circumcised or uncircumcised samples.

Although the research may eventually provide a clearer picture of the benefits or drawbacks of circumcision, it's too early to draw any conclusive results.

Circumcision may play a role in other health conditions

The human microbiome, which refers to the collection of microorganisms that live on and inside our bodies, is a relatively new and rapidly growing field of research.

While scientists have a good understanding of the gut microbiome and its role in health and disease, the penile microbiome is not as well-studied.

The penile microbiome is thought to play a role in a number of health conditions, including sexually transmitted infections and inflammation.

Studies have found that circumcised men are somewhat more protected from spreading bacterial vaginosis or contracting the human immunodeficiency virus (HIV/ AIDS).

Meta-analyses based on global data found that circumcision is linked to a reduction in bacterial infections, like syphilis, or viral infections, like genital herpes or herpes simplex virus type 2.

It's important to note that the protective effect of circumcision against these infections is not absolute. More research is needed to understand the full implications of this procedure.

The study was published in European Urology Focus.

Abstract:

Background: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome.

Objective: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism.

Design, setting, and participants: We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project.

Outcome measurements and statistical analysis: We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes–Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles.

Results and limitations: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision

Conclusions: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis.

Patient summary: 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. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.