Insertive vaginal sex is associated with altered penile immunology and enrichment of Gardnerella vaginalis in uncircumcised Ugandan men.

Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 8912860 Publication Model: Print Cited Medium: Internet ISSN: 1600-0897 (Electronic) Linking ISSN: 10467408 NLM ISO Abbreviation: Am J Reprod Immunol Subsets: MEDLINE

Publication: Copenhagen : Wiley-Blackwell
Original Publication: New York : Alan R. Liss, Inc., c1989-

Gardnerella vaginalis*/genetics ; Vaginosis, Bacterial*/microbiology; Male ; Female ; Humans ; Coitus ; Interleukin-8 ; RNA, Ribosomal, 16S/genetics ; Uganda/epidemiology ; Vagina/microbiology ; Bacteria/genetics ; Inflammation ; Cadherins

Problem: HIV susceptibility is linked to the penile immune milieu (particularly IL-8 levels) and microbiome. The effects of insertive vaginal sex itself on penile immunology and microbiota are not well described.
Method of Study: We compared the immune milieu and microbiology of the coronal sulcus (CS) and distal urethra in 47 uncircumcised Ugandan men reporting ever (n = 42) or never (n = 5) having had vaginal intercourse. Soluble immune factors were assayed by multiplex ELISA, and penile bacteria abundance by 16S rRNA qPCR and sequencing. Co-primary endpoints were penile levels of IL-8 and soluble E-cadherin.
Results: Independent of classical STIs, men reporting prior vaginal sex demonstrated elevated IL-8 levels in both the coronal sulcus (1.78 vs. 0.81 log10 pg/mL, p = .021) and urethra (2.93 vs. 2.30 log10 pg/mL; p = .003), with a strong inverse relationship between urethral IL-8 levels and the time from last vaginal sex (r = -0.436; p = .004). Vaginal sex was also associated with elevated penile IL-1α/β and soluble E-cadherin (sEcad), a marker of epithelial disruption. Gardnerella vaginalis (Gv) was only present in the penile microbiome of men reporting prior vaginal sex, and urethral Gv absolute abundance was strongly associated with urethral inflammation (r = 0.556; p < .001); corynebacteria were enriched in the CS of men reporting no prior vaginal sex and were associated with reduced CS inflammation.
Conclusions: Sexual intercourse was associated with sustained changes in penile immunology, potentially mediated through microbial alterations, in particular the urethral abundance of G. vaginalis. Future studies should further characterize the effects of sexual debut on penile bacteria and immunology.
(© 2023 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

AIDS. 2009 Jan 28;23(3):309-17. (PMID: 19114868)
Curr HIV/AIDS Rep. 2015 Jun;12(2):216-22. (PMID: 25877253)
Mucosal Immunol. 2013 Jul;6(4):776-86. (PMID: 23187317)
Microbiome. 2014 Feb 24;2(1):6. (PMID: 24558975)
Immunity. 2017 Jan 17;46(1):29-37. (PMID: 28087240)
Cell Rep Med. 2023 Mar 21;4(3):100981. (PMID: 36948151)
PLoS Med. 2012;9(6):e1001251. (PMID: 22745608)
PLoS Pathog. 2016 Nov 29;12(11):e1006025. (PMID: 27898732)
JCI Insight. 2021 Apr 22;6(8):. (PMID: 33884964)
Microbiome. 2016 Apr 19;4:16. (PMID: 27090518)
Microbiome. 2021 Dec 10;9(1):239. (PMID: 34893070)
Clin Infect Dis. 2015 Jul 15;61(2):260-9. (PMID: 25900168)
Microbiome. 2022 Jan 18;10(1):7. (PMID: 35042542)
Viruses. 2022 May 27;14(6):. (PMID: 35746636)
Mucosal Immunol. 2020 Jan;13(1):118-127. (PMID: 31619762)
Sex Transm Dis. 2013 Dec;40(12):944-9. (PMID: 24220356)
mBio. 2017 Jul 25;8(4):. (PMID: 28743816)
PLoS Pathog. 2022 Jan 4;18(1):e1009948. (PMID: 34982799)
Lancet Infect Dis. 2018 May;18(5):554-564. (PMID: 29396006)
Front Med (Lausanne). 2020 Jul 30;7:383. (PMID: 32850898)
J Clin Invest. 2022 Mar 15;132(6):. (PMID: 35113809)
mBio. 2015 Jun 16;6(3):e00589. (PMID: 26081632)
Am J Reprod Immunol. 2023 Mar;89(3):e13674. (PMID: 36593681)
Front Cell Infect Microbiol. 2022 Jul 05;12:916437. (PMID: 35865819)
Res Microbiol. 2015 Jun;166(5):440-447. (PMID: 25869222)
J Infect Dis. 2018 Aug 14;218(6):966-978. (PMID: 29718358)
PLoS One. 2012;7(5):e36298. (PMID: 22606251)
BMC Microbiol. 2012 Apr 17;12:56. (PMID: 22510143)
AIDS Res Ther. 2017 Sep 12;14(1):49. (PMID: 28893286)

D43 TW009578 United States TW FIC NIH HHS; R01 AI123002 United States AI NIAID NIH HHS; R01AI123002-01A1 United States NH NIH HHS; R01 AI128779 United States AI NIAID NIH HHS; R01 DK131936 United States DK NIDDK NIH HHS; R01AI128779 United States NH NIH HHS

Keywords: HIV susceptibility; microbiome; penile immunology; penile-vaginal sex

0 (Interleukin-8)
0 (RNA, Ribosomal, 16S)
0 (Cadherins)

Date Created: 20240129 Date Completed: 20240130 Latest Revision: 20250104

20250104

PMC10825315

10.1111/aji.13801

38282609