Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier
Open accessAbstract
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.
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BV-associated microbes compromise cervical epithelial barrier function that normally inhibits HPV entry to basal keratinocytes.
“It appears that through production of certain enzymes and metabolites, BV-associated microbes compromise the cervical epithelial barrier function that normally inhibits the entry of HPV to the basal keratinocytes (Borgdorff et al., 2016).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Borgdorff et al., 2016
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- Authors
- Borgdorff, H., Gautam, R., Armstrong, S. D., Xia, D., Ndayisaba, G. F., van Teijlingen, N. H., Geijtenbeek, T. B. H., Wastling, J. M., & van de Wijgert, J. H. H. M.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Liverpool (GB)
- Corresponding author
- Borgdorff, H
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 9
- Issue
- 3
- Pages
- 621-633
- ISSN
- 1933-0219 (ISSN-L)
- OpenAlex
- W1474461326
- Cited by
- 253
- References
- 57
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 42 · 2023: 31 · 2022: 34 · 2021: 26 · 2020: 28 · 2019: 19 · 2018: 17 · 2017: 15 · 2016: 7 · 2015: 1
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Keele Research Repository (Keele University) (submittedVersion, cc-by)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- Funders
- Aids Fonds
- European Commission (201102)
- University of Liverpool
- European and Developing Countries Clinical Trials Partnership
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- cervicovaginal microbiome, dysbiosis, mucosal barrier, female sex workers, HIV acquisition, Lactobacillus crispatus, Lactobacillus iners, mucus, MUC5B, MUC5AC, keratin, cornified envelope, lactate dehydrogenase, cell death, proteasome, antimicrobial peptides, inflammatory cytokines, immunoglobulins
- MeSH terms
- Lactobacillus crispatus, Adult, Female, Humans, Actin Cytoskeleton, Mucous Membrane, Mass Spectrometry, Vagina, HIV-1, HIV Infections, Cytokines, Disease Progression, Inflammation Mediators, Proteome, Microarray Analysis, Young Adult, Microbiota, Dysbiosis
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