title: The semen microbiome and its relationship with local immunology and viral load in HIV infection.
abstract: 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.
authors: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, United States of America; Center for Microbiomics and Human Health, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors: Cindy M
authors: CM
authors: Liu
authors: Department of Medicine, University of Toronto, Toronto, Canada.
authors: Brendan J W
authors: BJ
authors: Osborne
authors: Department of Biology, Northern Arizona University, Flagstaff, Arizona, United States of America.
authors: Bruce A
authors: BA
authors: Hungate
authors: Department of Medicine, University of Toronto, Toronto, Canada.
authors: Kamnoosh
authors: K
authors: Shahabi
authors: Department of Medicine, University of Toronto, Toronto, Canada.
authors: Sanja
authors: S
authors: Huibner
authors: Center for Microbiomics and Human Health, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors: Richard
authors: R
authors: Lester
authors: Center for Microbiomics and Human Health, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors: Michael G
authors: MG
authors: Dwan
authors: Department of Medicine, University of Toronto, Toronto, Canada; Maple Leaf Medical Centre, Toronto, Canada.
authors: Colin
authors: C
authors: Kovacs
authors: Center for Microbiomics and Human Health, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors: Tania L
authors: TL
authors: Contente-Cuomo
authors: Maple Leaf Medical Centre, Toronto, Canada.
authors: Erika
authors: E
authors: Benko
authors: Center for Microbiomics and Human Health, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America; Department of Environmental and Occupational Health, George Washington University School of Public Health, Washington, D.C., United States of America.
authors: Maliha
authors: M
authors: Aziz
authors: Center for Microbiomics and Human Health, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America; Department of Environmental and Occupational Health, George Washington University School of Public Health, Washington, D.C., United States of America.
authors: Lance B
authors: LB
authors: Price
authors: Department of Medicine, University of Toronto, Toronto, Canada; Department of Medicine, University Health Network, Toronto, Canada.
authors: Rupert
authors: R
authors: Kaul
mesh_terms: D000328:Adult; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy / Q000382:microbiology*; D015497:HIV-1; D006801:Humans; D008297:Male; D064307:Microbiota; D060737:Reproductive Tract Infections / Q000382:microbiology* / Q000821:virology; D012661:Semen / Q000382:microbiology*; D019562:Viral Load