Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier.
Vaginal microbiome (VMB) dysbiosis is associated with increased acquisition of HIV. Cervicovaginal inflammation and other changes to the mucosal barrier are thought to have important roles but human data are scarce. We compared the human cervicovaginal proteome by mass spectrometry of 50 Rwandan female sex workers who had previously been clustered into four VMB groups using a 16S phylogenetic microarray; in order of increasing bacterial diversity: Lactobacillus crispatus-dominated VMB (group 1), Lactobacillus iners-dominated VMB (group 2), moderate dysbiosis (group 3), and severe dysbiosis (group 4). We compared relative protein abundances among these VMB groups using targeted (abundance of pre-defined mucosal barrier proteins) and untargeted (differentially abundant proteins among all human proteins identified) approaches. With increasing bacterial diversity, we found: mucus alterations (increasing mucin 5B and 5AC), cytoskeleton alterations (increasing actin-organizing proteins; decreasing keratins and cornified envelope proteins), increasing lactate dehydrogenase A/B as markers of cell death, increasing proteolytic activity (increasing proteasome core complex proteins/proteases; decreasing antiproteases), altered antimicrobial peptide balance (increasing psoriasin, calprotectin, and histones; decreasing lysozyme and ubiquitin), increasing pro-inflammatory cytokines, and decreasing immunoglobulins immunoglobulin G1/2. Although temporal relationships cannot be derived, our findings support the hypothesis that dysbiosis causes cervicovaginal inflammation and other detrimental changes to the mucosal barrier.
Amsterdam Institute for Global Health and Development (AIGHD) and Department of Global Health, Academic Medical Center, Amsterdam, The Netherlands.
H
H
Borgdorff
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|Department of Health Management, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
R
R
Gautam
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
S D
SD
Armstrong
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
D
D
Xia
Rinda Ubuzima, Kigali, Rwanda.
G F
GF
Ndayisaba
Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
N H
NH
van Teijlingen
Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
T B H
TB
Geijtenbeek
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
J M
JM
Wastling
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|Rinda Ubuzima, Kigali, Rwanda.
J H H M
JH
van de Wijgert
D008841:Actin Cytoskeleton / Q000378:metabolism; D000328:Adult; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000070003:Lactobacillus crispatus / Q000276:immunology*; D013058:Mass Spectrometry; D046228:Microarray Analysis; D064307:Microbiota / Q000502:physiology*; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D020543:Proteome; D014621:Vagina / Q000276:immunology / Q000382:microbiology*; D055815:Young Adult
D016207:Cytokines; D018836:Inflammation Mediators; D020543:Proteome