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

Study information

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

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

25058515

DOI Digital object identifier for electronic documents.

10.1371/journal.ppat.1004262

URI

https://pubmed.ncbi.nlm.nih.gov/25058515/

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

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

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): Joyessa, Claregrieve1, WikiWorks, Victoria

Subjects

Location of subjects: Canada

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: Semen Ejaculate,Sperm,Semen,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),hIV infection

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: 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

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

Statistical test: 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

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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	Quality Control	Links
Bifidobacterium
Enhydrobacter
Pseudonocardia
Geodermatophilaceae
Micromonosporaceae
Massilia
Erwinia
Leifsonia
Acidovorax
Friedmanniella
Nakamurellaceae
Acinetobacter
Bacillus
Actinomycetales
unclassified Bacteroidota
Burkholderiales
Variovorax
Rhodobacterales
Nostocoides
Oscillospiraceae
Hymenobacter
Rhodoferax