Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility

• DOI: 10.1186/s40168-021-01185-9
• Publication Date: 2022-01-18T09:17:53Z
• Authors: Ronald M. Galiwango; Daniel E. Park; Sanja Huibner; Abigail Onos; Maliha Aziz; Kelsey Roach; Aggrey Anok; James Nnamutete; Yahaya Isabirye; John Bosco Wasswa; Deo Male; Godfrey Kigozi; Aaron A. R. Tobian; Jessica L. Prodger; Cindy M. Liu; Rupert Kaul
• Keywords: Sex organ

Coronal sulcus (CS) anaerobe abundance and IL-8 levels are linked to HIV acquisition, dramatically reduced after penile circumcision (PC). The distal urethra may be the site of some acquisition before PC, presumably most post PC. We describe immune milieu microbiome in uncircumcised Ugandan men, define impact Participants consisted HIV-negative, genital symptom-free adult men undergoing PC (n = 51). Urethral coronal swabs were collected at baseline 6- 12-months post-PC. Soluble factors quantified by multiplex ELISA, bacterial assessed 16S rRNA qPCR sequencing.At baseline, was enriched compared CS for cytokines (including MIP-1β) soluble E-cadherin (sE-cadherin, an epithelial disruption marker), although IL-1α IL-1β higher. Baseline total ≥ 20-fold higher than (median 27,100 vs. 1200 gene copies/swab, p 0.001), anaerobes comprised 58% bacteria 42% urethral bacteria. did not alter 806 1130 pg/ml 12 months; 0.062) sE-cadherin increased (113,223 158,385 pg/ml, 0.009), despite five- sevenfold drops respectively. However, (15,843 837 < 0.001) (IL-8; 34 3 while reducing 13-fold 60-fold, respectively (both P ≤ 0.004).The is immunologically rich with characteristics HIV-susceptible tissue site. had no on immunology have integrity, modest reductions anaerobes, suggesting that protection from mediated via or alterations urethra. Video abstract.