Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.

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.

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

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.

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.

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.

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.

European urology focus. 2022 Dec 22 [Epub ahead of print]

Kirtishri Mishra, Ilaha Isali, Mohit Sindhani, Megan Prunty, Spencer Bell, Amr Mahran, Giovanni Damiani, Mahmoud Ghannoum, Mauricio Retuerto, Alexander Kutikov, Jonathan Ross, Lynn L Woo, Philip H Abbosh, Laura Bukavina

Department of Urology, New York University, Langone Medical Center, New York, NY, USA; Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA., Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA., Indian Institute of Technology, Delhi, India., Fox Chase Cancer Center, Philadelphia, PA, USA., Department of Urology, University of Tennessee, Knoxville, TN, USA; Department of Urology, Assiut University, Assiut, Egypt., Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy., Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Case Western Reserve School of Medicine, Center for Medical Mycology, Cleveland, OH, USA., Case Western Reserve School of Medicine, Center for Medical Mycology, Cleveland, OH, USA., Department of Urology, Rush University, Chicago, IL, USA., Einstein Medical Center, Department of Urology, Philadelphia, PA, USA., Fox Chase Cancer Center, Philadelphia, PA, USA; Department of Urology, Rainbow Babies and Children's Hospital, Cleveland, OH, USA., Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA; Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address: .

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