Abstract
The foreskin is a site of heterosexual acquisition of HIV-1 among uncircumcised men. However, some men remain HIV-negative despite repeated, unprotected vaginal intercourse with HIV-positive partners, while others become infected after few exposures. The foreskin microbiome includes a diverse group of anaerobic bacteria that have been linked to HIV acquisition. However, these anaerobes tend to coassociate, making it difficult to determine which species might increase HIV risk and which may be innocent bystanders. Here, we show that 6 specific anaerobic bacterial species, Peptostreptococcus anaerobius, Prevotella bivia, Prevotella disiens, Dialister propionicifaciens, Dialister micraerophilus, and a genetic near neighbor of Dialister succinatiphilus, significantly increased cytokine production, recruited HIV-susceptible CD4+ T cells to the inner foreskin, and were associated with HIV acquisition. This strongly suggests that the penile microbiome increases host susceptibility to HIV and that these species are potential targets for microbiome-based prevention strategies.
Highlights
1.7 million people are newly infected by HIV-1 each year [1]
We initially performed a comprehensive assessment of foreskin bacterial communities from HIV-uninfected men, using coronal sulcus swabs collected from men in the uncircumcised control arm of a randomized trial of male circumcision for HIV prevention in Rakai, Uganda [6]
The foreskin is the major site of HIV acquisition in uncircumcised heterosexual men, and HIV risk is reduced by almost 60% after penile circumcision [6,7,8]
Summary
1.7 million people are newly infected by HIV-1 each year [1]. The composition of the bacterial community on the foreskin modifies a heterosexual man’s risk for HIV acquisition [2], as is the case for the vaginal bacterial community in a woman [3, 4], and may contribute to the well-established protective effect of male circumcision [5,6,7,8]. The bacterial species responsible for increased HIV risk and the biological mechanism by which they facilitate HIV acquisition are unclear. Closing these knowledge gaps may open doors for novel HIV prevention strategies. Microbes can activate immune cells, making them more susceptible to HIV; the bacterial species that comprise the foreskin microbiome may be a key determinant of HIV susceptibility. We present for the first time, to our knowledge, a comprehensive analysis of the penile bacterial microbiome in 2 previously described, independent cohorts of HIV-uninfected and uncircumcised men from rural Uganda [6, 10] in order to identify the exact foreskin bacterial species associated with enhanced HIV acquisition and to determine whether these species drive HIV acquisition by recruiting HIV-susceptible CD4+ T cells to vulnerable regions of the inner foreskin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
