Compositional and functional differences of the vaginal microbiota of women with and without cervical dysplasia.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 05 2024
16 05 2024
Historique:
received:
29
01
2024
accepted:
12
05
2024
medline:
17
5
2024
pubmed:
17
5
2024
entrez:
16
5
2024
Statut:
epublish
Résumé
Alterations in the vaginal microbiota, including both species composition and functional pathways, have been associated with HPV infection and progression of dysplasia to cervical cancer. To further explore this, shotgun metagenomic sequencing was used to taxonomically and functionally characterize the vaginal microbiota of women with and without cervical dysplasia. Women with histologically verified dysplasia (n = 177; low grade dysplasia (LSIL) n = 81, high-grade dysplasia (HSIL) n = 94, cancer n = 2) were compared with healthy controls recruited from the cervical screening programme (n = 177). Women with dysplasia had a higher vaginal microbial diversity, and higher abundances of Gardnerella vaginalis, Aerococcus christensenii, Peptoniphilus lacrimalis and Fannyhessea vaginae, while healthy controls had higher relative abundance of Lactobacillus crispatus. Genes involved in e.g. nucleotide biosynthesis and peptidoglycan biosynthesis were more abundant in women with dysplasia. Healthy controls showed higher abundance of genes important for e.g. amino acid biosynthesis, (especially L-lysine) and sugar degradation. These findings suggest that the microbiota may have a role in creating a pro-oncogenic environment in women with dysplasia. Its role and potential interactions with other components in the microenvironment deserve further exploration.
Identifiants
pubmed: 38755259
doi: 10.1038/s41598-024-61942-2
pii: 10.1038/s41598-024-61942-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11183Subventions
Organisme : SciLifeLab & Wallenberg Data Driven Life Science Program
ID : KAW 2020.0239
Informations de copyright
© 2024. The Author(s).
Références
Dunne, E. F. et al. Prevalence of HPV infection among females in the United States. JAMA 297(8), 813–819 (2007).
pubmed: 17327523
doi: 10.1001/jama.297.8.813
Plummer, M. et al. A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J. Infect. Dis. 195(11), 1582–9 (2007).
pubmed: 17471427
doi: 10.1086/516784
Ferlay, J. et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer 144(8), 1941–1953 (2019).
pubmed: 30350310
doi: 10.1002/ijc.31937
zur Hausen, H. Viruses in human cancers. Eur. J. Cancer 35(14), 1878–85 (1999).
pubmed: 10711230
doi: 10.1016/S0959-8049(99)00291-9
Who, Comprehensive cervical cancer control: A guide to essential practice. (2014).
Aroutcheva, A. et al. Defense factors of vaginal lactobacilli. Am. J. Obstet. Gynecol. 185(2), 375–379 (2001).
pubmed: 11518895
doi: 10.1067/mob.2001.115867
Ravel, J. et al. Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA 108(Suppl 1), 4680–4687 (2011).
pubmed: 20534435
doi: 10.1073/pnas.1002611107
Boris, S. & Barbés, C. Role played by lactobacilli in controlling the population of vaginal pathogens. Microbes Infect. 2(5), 543–546 (2000).
pubmed: 10865199
doi: 10.1016/S1286-4579(00)00313-0
Norenhag, J. et al. The vaginal microbiota, HPV and cervical dysplasia: A systematic review and network meta-analysis. Int. J. Obstet. Gynaecol. 127, 171–180 (2019).
doi: 10.1111/1471-0528.15854
Brotman, R. M. et al. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. J. Infect. Dis. 210(11), 1723–1733 (2014).
pubmed: 24943724
pmcid: 4296189
doi: 10.1093/infdis/jiu330
Mitra, A. et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci. Rep. 5, 16865 (2015).
pubmed: 26574055
pmcid: 4648063
doi: 10.1038/srep16865
Mitra, A. et al. The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions. Nat. Commun. 11(1), 1999 (2020).
pubmed: 32332850
pmcid: 7181700
doi: 10.1038/s41467-020-15856-y
Maarsingh, J. D., Łaniewski, P. & Herbst-Kralovetz, M. M. Immunometabolic and potential tumor-promoting changes in 3D cervical cell models infected with bacterial vaginosis-associated bacteria. Commun. Biol. 5(1), 725 (2022).
pubmed: 35869172
pmcid: 9307755
doi: 10.1038/s42003-022-03681-6
Hanahan, D. Hallmarks of cancer: New dimensions. Cancer Discov. 12(1), 31–46 (2022).
pubmed: 35022204
doi: 10.1158/2159-8290.CD-21-1059
Kwon, M., Seo, S. S., Kim, M. K., Lee, D. O. & Lim, M. C. Compositional and functional differences between microbiota and cervical carcinogenesis as identified by shotgun metagenomic sequencing. Cancers (Basel) 11(3), 309 (2019).
pubmed: 30841606
doi: 10.3390/cancers11030309
Liu, H., Liang, H., Li, D., Wang, M. & Li, Y. Association of cervical dysbacteriosis, HPV oncogene expression, and cervical lesion progression. Microbiol. Spectr. 10(5), e0015122 (2022).
pubmed: 36036584
doi: 10.1128/spectrum.00151-22
France, M. T. et al. VALENCIA: A nearest centroid classification method for vaginal microbial communities based on composition. Microbiome 8(1), 166 (2020).
pubmed: 33228810
pmcid: 7684964
doi: 10.1186/s40168-020-00934-6
Audirac-Chalifour, A. et al. Cervical microbiome and cytokine profile at various stages of cervical cancer: A pilot study. Plos One. 11(4), e015274 (2016).
doi: 10.1371/journal.pone.0153274
Fredricks, D. N., Fiedler, T. L. & Marrazzo, J. M. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 353(18), 1899–1911 (2005).
pubmed: 16267321
doi: 10.1056/NEJMoa043802
Łaniewski, P. & Herbst-Kralovetz, M. M. Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix. NPJ Biofilms Microbiomes 7(1), 88 (2021).
pubmed: 34903740
pmcid: 8669023
doi: 10.1038/s41522-021-00259-8
Di Pietro, M. et al. HPV/Chlamydia trachomatis co-infection: Metagenomic analysis of cervical microbiota in asymptomatic women. New Microbiol. 41(1), 34–41 (2018).
pubmed: 29313867
Di Paola, M. et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection. Sci. Rep. 7(1), 10200 (2017).
pubmed: 28860468
pmcid: 5579045
doi: 10.1038/s41598-017-09842-6
Lin, W. et al. Changes of the vaginal microbiota in HPV infection and cervical intraepithelial neoplasia: a cross-sectional analysis. Sci. Rep. 12(1), 2812 (2022).
pubmed: 35181685
pmcid: 8857277
doi: 10.1038/s41598-022-06731-5
Pramanick, R., Nathani, N., Warke, H., Mayadeo, N. & Aranha, C. Vaginal dysbiotic microbiome in women with no symptoms of genital infections. Front. Cell. Infect. Microbiol. 11, 760459 (2021).
pubmed: 35096634
doi: 10.3389/fcimb.2021.760459
Kowalik, M. A., Columbano, A. & Perra, A. Emerging role of the pentose phosphate pathway in hepatocellular carcinoma. Front. Oncol. 7, 87 (2017).
pubmed: 28553614
pmcid: 5425478
doi: 10.3389/fonc.2017.00087
Jiang, P., Du, W. & Wu, M. Regulation of the pentose phosphate pathway in cancer. Protein Cell. 5(8), 592–602 (2014).
pubmed: 25015087
pmcid: 4112277
doi: 10.1007/s13238-014-0082-8
Fettweis, J. M. et al. The vaginal microbiome and preterm birth. Nat. Med. 25(6), 1012–1021 (2019).
pubmed: 31142849
pmcid: 6750801
doi: 10.1038/s41591-019-0450-2
Bagheri, P., Hoang, K., Fung, A. A., Hussain, S. & Shi, L. Visualizing cancer cell metabolic dynamics regulated with aromatic amino acids using DO-SRS and 2PEF microscopy. Front. Mol. Biosci. 8, 779702 (2021).
pubmed: 34977157
pmcid: 8714916
doi: 10.3389/fmolb.2021.779702
Huang, K. et al. Salivary microbiota for gastric cancer prediction: an exploratory study. Front. Cell. Infect. Microbiol. 11, 640309 (2021).
pubmed: 33777850
pmcid: 7988213
doi: 10.3389/fcimb.2021.640309
Nie, S., Wang, A. & Yuan, Y. Comparison of clinicopathological parameters, prognosis, micro-ecological environment and metabolic function of Gastric Cancer with or without Fusobacterium sp. Infection. J Cancer. 12(4), 1023–1032 (2021).
pubmed: 33442401
doi: 10.7150/jca.50918
Mollick, T. & Laín, S. Modulating pyrimidine ribonucleotide levels for the treatment of cancer. Cancer Metab. 8, 12 (2020).
pubmed: 33020720
pmcid: 7285601
doi: 10.1186/s40170-020-00218-5
Evans, D. R. & Guy, H. I. Mammalian pyrimidine biosynthesis: Fresh insights into an ancient pathway. J. Biol. Chem. 279(32), 33035–33038 (2004).
pubmed: 15096496
doi: 10.1074/jbc.R400007200
De Vitto, H., Arachchige, D. B., Richardson, B. C. & French, J. B. The Intersection of Purine and Mitochondrial Metabolism in Cancer. Cells 10(10), 2603 (2021).
pubmed: 34685583
pmcid: 8534091
doi: 10.3390/cells10102603
Zhang, Y. et al. L-lysine ameliorates sepsis-induced acute lung injury in a lipopolysaccharide-induced mouse model. Biomed. Pharmacother. 118, 109307 (2019).
pubmed: 31404772
doi: 10.1016/j.biopha.2019.109307
Zhang, C., He, Y. & Shen, Y. L-Lysine protects against sepsis-induced chronic lung injury in male albino rats. Biomed. Pharmacother. 117, 109043 (2019).
pubmed: 31238259
doi: 10.1016/j.biopha.2019.109043
Mosca, L. et al. Effects of S-adenosyl-L-methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms. Int. J. Oncol. 56(5), 1212–1224 (2020).
pubmed: 32319579
pmcid: 7115356
Wojcieszyńska, D., Hupert-Kocurek, K. & Guzik, U. Flavin-dependent enzymes in cancer prevention. Int. J. Mol. Sci. 13(12), 16751–16768 (2012).
pubmed: 23222680
pmcid: 3546718
doi: 10.3390/ijms131216751
Manzoor, A. et al. Characterization of the gastrointestinal and reproductive tract microbiota in fertile and infertile Pakistani couples. Biology (Basel) 11(1), 40 (2021).
pubmed: 35053038
Sangha, A. K. & Kantidakis, T. The Aminoacyl-tRNA Synthetase and tRNA expression levels are deregulated in cancer and correlate independently with patient survival. Curr. Issues Mol. Biol. 44(7), 3001–3017 (2022).
pubmed: 35877431
pmcid: 9324904
doi: 10.3390/cimb44070207
Li, C. J. et al. Acetyl coenzyme A synthase 2 acts as a prognostic biomarker associated with immune infiltration in cervical squamous cell carcinoma. Cancers (Basel). 13(13), 3125 (2021).
pubmed: 34206705
pmcid: 8269092
doi: 10.3390/cancers13133125
Lévy, P. & Bartosch, B. Metabolic reprogramming: A hallmark of viral oncogenesis. Oncogene 35(32), 4155–4164 (2016).
pubmed: 26686092
doi: 10.1038/onc.2015.479
Pal, A. & Kundu, R. Human papillomavirus E6 and E7: The cervical cancer hallmarks and targets for therapy. Front Microbiol. 10, 3116 (2019).
pubmed: 32038557
doi: 10.3389/fmicb.2019.03116
Bhatt, A. P., Redinbo, M. R. & Bultman, S. J. The role of the microbiome in cancer development and therapy. CA Cancer J. Clin. 67(4), 326–344 (2017).
pubmed: 28481406
pmcid: 5530583
doi: 10.3322/caac.21398
Garrett, W. S. Cancer and the microbiota. Science 348(6230), 80–86 (2015).
pubmed: 25838377
pmcid: 5535753
doi: 10.1126/science.aaa4972
Jimenez, N. R., Maarsingh, J. D., Łaniewski, P. & Herbst-Kralovetz, M. M. Commensal lactobacilli metabolically contribute to cervical epithelial homeostasis in a species-specific manner. mSphere 8(1), e0045222 (2023).
pubmed: 36629413
doi: 10.1128/msphere.00452-22
Machado, A. & Cerca, N. Influence of biofilm formation by gardnerella vaginalis and other anaerobes on bacterial vaginosis. J. Infect. Dis. 212(12), 1856–1861 (2015).
pubmed: 26080369
doi: 10.1093/infdis/jiv338
Swidsinski, A. et al. Adherent biofilms in bacterial vaginosis. Obstet. Gynecol. 106(5 Pt 1), 1013–1023 (2005).
pubmed: 16260520
doi: 10.1097/01.AOG.0000183594.45524.d2
Swidsinski, A. et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol. Histopathol. 29(5), 567–587 (2014).
pubmed: 24327088
Amsel, R. et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am. J. Med. 74(1), 14–22 (1983).
pubmed: 6600371
doi: 10.1016/0002-9343(83)91112-9
Wu, S. et al. The feature of cervical microbiota associated with the progression of cervical cancer among reproductive females. Gynecol. Oncol. 163(2), 348–357 (2021).
pubmed: 34503848
doi: 10.1016/j.ygyno.2021.08.016
Smith, J. S. et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Int. J. Cancer 121(3), 621–632 (2007).
pubmed: 17405118
doi: 10.1002/ijc.22527
Brusselaers, N., Shrestha, S., van de Wijgert, J. & Verstraelen, H. Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: Systematic review and meta-analysis. Am. J. Obstet. Gynecol. 221(1), 9-18.e8 (2019).
pubmed: 30550767
doi: 10.1016/j.ajog.2018.12.011
Verhoeven, V. et al. Probiotics enhance the clearance of human papillomavirus-related cervical lesions: A prospective controlled pilot study. Eur. J. Cancer Prev. 22(1), 46–51 (2013).
pubmed: 22706167
doi: 10.1097/CEJ.0b013e328355ed23
Palma, E. et al. Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: A promising solution against HPV-infection. BMC Infect. Dis. 18(1), 13 (2018).
pubmed: 29304768
pmcid: 5756375
doi: 10.1186/s12879-017-2938-z
Ho, D., Imai, K., King, G. & Stuart, E. A. MatchIt: Nonparametric preprocessing for parametric causal inference. J. Statist. Softw. https://doi.org/10.18637/jss.v042.i08 (2011).
doi: 10.18637/jss.v042.i08
Hugerth, L. W. et al. Assessment of In vitro and in silico protocols for sequence-based characterization of the human vaginal microbiome. mSphere https://doi.org/10.1128/mSphere.01253-20 (2020).
doi: 10.1128/mSphere.01253-20
pubmed: 33361132
pmcid: 7763557
Gustavsson, I. et al. Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening. Virol. J. 16(1), 107 (2019).
pubmed: 31438976
pmcid: 6704622
doi: 10.1186/s12985-019-1216-7
Wood, D. E., Lu, J. & Langmead, B. Improved metagenomic analysis with Kraken 2. Genome Biol. 20(1), 257 (2019).
pubmed: 31779668
pmcid: 6883579
doi: 10.1186/s13059-019-1891-0
Beghini, F. et al. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. Elife https://doi.org/10.7554/eLife.65088 (2021).
doi: 10.7554/eLife.65088
pubmed: 33944776
pmcid: 8096432
Davis, N. M., Proctor, D. M., Holmes, S. P., Relman, D. A. & Callahan, B. J. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 6(1), 226 (2018).
pubmed: 30558668
pmcid: 6298009
doi: 10.1186/s40168-018-0605-2
Oksanen, J., Simpson, G., Blanchet, F., Kindt, R., Legendre, P., Minchin, P., et al. Vegan: Community Ecology Package. R package version 26–52023.
Nearing, J. T. et al. Microbiome differential abundance methods produce different results across 38 datasets. Nat. Commun. 13(1), 342 (2022).
pubmed: 35039521
pmcid: 8763921
doi: 10.1038/s41467-022-28034-z
Fernandes, A. D., Macklaim, J. M., Linn, T. G., Reid, G. & Gloor, G. B. ANOVA-like differential expression (ALDEx) analysis for mixed population RNA-Seq. PLoS One 8(7), e67019 (2013).
pubmed: 23843979
pmcid: 3699591
doi: 10.1371/journal.pone.0067019
García, F. R. et al. Prevalence of the human papillomavirus (HPV) types among cervical dysplasia women attending a gynaecological clinic in Sweden. BJC Rep. 34, 1986 (2023).
Hao, Y. et al. HPViewer: Sensitive and specific genotyping of human papillomavirus in metagenomic DNA. Bioinformatics 34(12), 1986–1995 (2018).
pubmed: 29377990
pmcid: 6658710
doi: 10.1093/bioinformatics/bty037
Bihl, M. P. et al. Human papillomavirus (HPV) detection in cytologic specimens: Similarities and differences of available methodology. Appl. Immunohistochem. Mol. Morphol. 25(3), 184–189 (2017).
pubmed: 26580098
pmcid: 5359783
doi: 10.1097/PAI.0000000000000290
Schmitt, M. et al. Bead-based multiplex genotyping of human papillomaviruses. J. Clin. Microbiol. 44(2), 504–512 (2006).
pubmed: 16455905
pmcid: 1392679
doi: 10.1128/JCM.44.2.504-512.2006
Muñoz, N. et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N. Engl. J. Med. 348(6), 518–527 (2003).
pubmed: 12571259
doi: 10.1056/NEJMoa021641