Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Microbiome
Abstract
Coronal sulcus (CS) anaerobe abundance and IL-8 levels are linked to HIV acquisition, and are dramatically
reduced after penile circumcision (PC). The distal urethra may be the site of some HIV acquisition before PC,
and presumably most acquisition post PC. We describe the immune milieu and microbiome of the distal urethra in
uncircumcised Ugandan men, and define the impact of PC. Participants consisted of HIV-negative, genital symptomfree
adult Ugandan men undergoing PC (n = 51). Urethral and coronal sulcus swabs were collected at baseline and
at 6- and 12-months post-PC. Soluble immune factors were quantified by multiplex ELISA, and bacterial abundance
assessed by 16S rRNA qPCR and sequencing.
Results: At baseline, the urethra was enriched compared to the CS for most cytokines (including IL-8 and MIP-1β)
and soluble E-cadherin (sE-cadherin, an epithelial disruption marker), although CS levels of IL-1α and IL-1β were
higher. Baseline total bacterial abundance was ≥ 20-fold higher in the CS than the urethra (median 27,100 vs. 1200
gene copies/swab, p = 0.001), and anaerobes comprised 58% of CS bacteria vs. 42% of urethral bacteria. PC did not
alter urethral IL-8 (median 806 at baseline vs. 1130 pg/ml at 12 months; p = 0.062) and urethral sE-cadherin increased
(113,223 vs. 158,385 pg/ml, p = 0.009), despite five- and sevenfold drops in total bacterial and anaerobe abundance
after PC, respectively. However, PC dramatically reduced CS levels of sE-cadherin (15,843 vs. 837 pg/ml, p < 0.001) and
most cytokines (IL-8; 34 vs. 3 pg/ml, p < 0.001), while reducing total bacterial and anaerobe abundance by 13-fold and
60-fold, respectively (both P ≤ 0.004).
Conclusions: The urethra is immunologically rich with characteristics of an HIV-susceptible tissue site. However, PC
had no impact on urethral immunology and may have reduced epithelial integrity, despite modest reductions in total
bacteria and anaerobes, suggesting that HIV protection from PC is not mediated via immune or microbiome alterations
in the urethra.
Description
Keywords
Microbiome, Cytokines, Coronal sulcus, Penile urethra, Penile circumcision, Uganda, HIV
Citation
Galiwango, R. M., Park, D. E., Huibner, S., Onos, A., Aziz, M., Roach, K., ... & Kaul, R. (2022). Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility. Microbiome, 10(1), 1-13. https://doi.org/10.1186/s40168-021-01185-9