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

From BugSigDB
Needs review
study design
case-control
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


Needs review

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): WikiWorks753, Joyessa

Subjects

Location of subjects Country from which study subjects were recruited
United States of America
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
Semen bacterial burden was associated with seven pro-inflammatory semen cytokines in HIV-infected men, including IL-6 (p = 0.024), TNF-a (p = 0.009), and IL-1b (p = 0.002). Semen VL was linked to IL-1b in particular (r2 = 0.18, p = 0.02). The bacterial load in the sperm was likewise connected to the HIV VL in the sperm (r2 = 0.15, p = 0.02). HIV infection changes the interaction between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, implying that the semen microbiome may play a role in HIV transmission.
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

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)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): Joyessa

Source: Table 2

Description: Streptococcus, Corynebacterium, and Staphylococcus were among the most common and proportionally abundant semen bacteria among HIV-uninfected MSM. Prevotella, Porphyromonas, Finegoldia, Micrococcus, and Actinomyces were among the bacteria that were proportionately abundant and made up 1–3% of the semen microbiota. While Ureaplasma was only found in four males, it made up a significant component of their semen microbiome. Regardless of HIV status, Streptococcus was the most common bacterium in sperm. Prior to starting antiretroviral therapy, the prevalence and proportional abundances of the 40 most common semen germs in uninfected men and HIV-infected males.

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

NCBI Links
Bifidobacterium
Enhydrobacter
Pseudonocardia

Revision editor(s): Joyessa

Signature 2

Needs review

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): Joyessa

Source: Figure 1

Description: Streptococcus, Corynebacterium, and Staphylococcus were among the most common and proportionally abundant semen bacteria among HIV-uninfected MSM. Prevotella, Porphyromonas, Finegoldia, Micrococcus, and Actinomyces were among the bacteria that were proportionately abundant and made up 1–3% of the semen microbiota. Even though Ureaplasma was only found in four males, it made up a significant component of the semen microbiome. In HIV-positive men, the proportionate abundance of Mycoplasma reduced over time. Richness refers to how far the plot extends along the x-axis, whereas evenness refers to how steep the slope is. A high y-intercept indicates extreme dominance. The HIV uninfected has a richer and more even relationship than the ART-naive, but the relationship converges on the HIV uninfected after 6 months of ART.

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

NCBI Links
Mycoplasma
Prevotella
Sneathia
Streptococcus

Revision editor(s): Joyessa