Penile Anaerobic Dysbiosis as a Risk Factor for HIV Infection

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

28743816

DOI Digital object identifier for electronic documents.

10.1128/mBio.00996-17

URI

https://pubmed.ncbi.nlm.nih.gov/28743816/

Authors

Liu CM, Prodger JL, Tobian AAR, Abraham AG, Kigozi G, Hungate BA, Aziz M, Nalugoda F, Sariya S, Serwadda D, Kaul R, Gray RH, Price LB

Journal

mBio

Year

2017

Keywords:

anaerobes, cytokines, foreskin inflammation, human immunodeficiency virus, penile microbiome, susceptibility

Sexual transmission of HIV requires exposure to the virus and infection of activated mucosal immune cells, specifically CD4+ T cells or dendritic cells. The foreskin is a major site of viral entry in heterosexual transmission of HIV. Although the probability of acquiring HIV from a sexual encounter is low, the risk varies even after adjusting for known HIV risk factors. The genital microbiome may account for some of the variability in risk by interacting with the host immune system to trigger inflammatory responses that mediate the infection of mucosal immune cells. We conducted a case-control study of uncircumcised participants nested within a randomized-controlled trial of male circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by study personnel at trial enrollment, we characterized the penile microbiome by sequencing and real-time PCR and cytokine levels by electrochemiluminescence assays. The absolute abundances of penile anaerobes at enrollment were associated with later risk of HIV seroconversion, with a 10-fold increase in Prevotella, Dialister, Finegoldia, and Peptoniphilus increasing the odds of HIV acquisition by 54 to 63%, after controlling for other known HIV risk factors. Increased abundances of anaerobic bacteria were also correlated with increased cytokines, including interleukin-8, which can trigger an inflammatory response that recruits susceptible immune cells, suggesting a mechanism underlying the increased risk. These same anaerobic genera can be shared between heterosexual partners and are associated with increased HIV acquisition in women, pointing to anaerobic dysbiosis in the genital microbiome and an accompanying inflammatory response as a novel, independent, and transmissible risk factor for HIV infection.IMPORTANCE We found that uncircumcised men who became infected by HIV during a 2-year clinical trial had higher levels of penile anaerobes than uncircumcised men who remained HIV negative. We also found that having higher levels of penile anaerobes was also associated with higher production of immune factors that recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes are known to be shared by heterosexual partners and are associated with HIV risk in women. Therefore, penile anaerobes may be a sexually transmissible risk factor for HIV, and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/08/31

Curated date: 2022/01/12

Curator: Joyessa

Revision editor(s): WikiWorks, Claregrieve1, Joyessa, Peace Sandy

Subjects

Location of subjects: Uganda

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Skin of penis Penile skin,Penis skin,Penis zone of skin,Zone of skin of penis,Skin of penis,skin of penis

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HIV seronegative

Group 1 name Corresponds to the case (exposed) group for case-control studies: HIV seroconverted

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HIV-infected trial participants who were randomized to the delayed circumcision arm of the trial and remained uncircumcised who seroconverted during the trial

Group 0 sample size Number of subjects in the control (unexposed) group: 136

Group 1 sample size Number of subjects in the case (exposed) group: 46

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 24 months.

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances