Penile Anaerobic Dysbiosis as a Risk Factor for HIV Infection

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022
study design
case-control
Citation
PMID
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
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


Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022

Curated date: 2022/01/12

Curator: Joyessa

Revision editor(s): WikiWorks753, Joyessa, Claregrieve1

Subjects

Location of subjects Country from which study subjects were recruited
Uganda
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder)
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 Experimental technique used for quantifying microbial abundance
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

Statistical test Statistical test or computational tool used for differential abundance testing
PERMANOVA
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No



Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022

Curated date: 2022/01/12

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1

Source: Table S1

Description: Differential microbial abundance between HIV seroconverters and HIV-negative controls

Abundance in Group 1: increased abundance in HIV seroconverted

NCBI Links
Dialister
Mobiluncus
Peptostreptococcus

Revision editor(s): Joyessa, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022

Curated date: 2022/01/12

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1

Source: Table S1

Description: Differential microbial abundance between HIV seroconverters and HIV-negative controls

Abundance in Group 1: decreased abundance in HIV seroconverted

NCBI Links
Prevotella
Murdochiella

Revision editor(s): Joyessa, Claregrieve1