The semen microbiome and its relationship with local immunology and viral load in HIV infection

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022
study design
time series / longitudinal observational
Citation
PMID
Authors
Liu CM, Osborne BJ, Hungate BA, Shahabi K, Huibner S, Lester R, Dwan MG, Kovacs C, Contente-Cuomo TL, Benko E, Aziz M, Price LB, Kaul R
Journal
PLoS pathogens
Year
2014
Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r(2)  = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r(2) = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): WikiWorks753, Joyessa, Claregrieve1

Subjects

Location of subjects Country from which study subjects were recruited
Canada
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
Semen Ejaculate,Sperm,Semen
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-uninfected men
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-infected men
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
MSM with HIV infection
Group 0 sample size Number of subjects in the control (unexposed) group
22
Group 1 sample size Number of subjects in the case (exposed) group
27
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 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-V6
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
ANOVA
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
Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1

Source: Table S2

Description: Differential microbial abundance between HIV- and HIV+ men

Abundance in Group 1: decreased abundance in HIV-infected men

NCBI Links
Bifidobacterium
Enhydrobacter
Pseudonocardia
Geodermatophilaceae
Micromonosporaceae
Massilia
Erwinia
Leifsonia
Acidovorax
Friedmanniella
Nakamurellaceae
Acinetobacter
Bacillus
Actinomycetales
unclassified Bacteroidetes
Burkholderiales
Variovorax
Rhodobacterales
Tetrasphaera
Oscillospiraceae
Hymenobacter
Rhodoferax

Revision editor(s): Joyessa, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 31 August 2022

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1

Source: Table S2

Description: Differential microbial abundance between HIV- and HIV+ men

Abundance in Group 1: increased abundance in HIV-infected men

NCBI Links
Veillonella
Actinomycetospora

Revision editor(s): Joyessa, Claregrieve1