Skip to main content
Top
Published in: BMC Infectious Diseases 1/2015

Open Access 01-12-2015 | Research article

Correlates of the molecular vaginal microbiota composition of African women

Authors: Raju Gautam, Hanneke Borgdorff, Vicky Jespers, Suzanna C Francis, Rita Verhelst, Mary Mwaura, Sinead Delany-Moretlwe, Gilles Ndayisaba, Jordan K Kyongo, Liselotte Hardy, Joris Menten, Tania Crucitti, Evgeni Tsivtsivadze, Frank Schuren, Janneke HHM van de Wijgert, for the Vaginal Biomarkers Study Group

Published in: BMC Infectious Diseases | Issue 1/2015

Login to get access

Abstract

Background

Sociodemographic, behavioral and clinical correlates of the vaginal microbiome (VMB) as characterized by molecular methods have not been adequately studied. VMB dominated by bacteria other than lactobacilli may cause inflammation, which may facilitate HIV acquisition and other adverse reproductive health outcomes.

Methods

We characterized the VMB of women in Kenya, Rwanda, South Africa and Tanzania (KRST) using a 16S rDNA phylogenetic microarray. Cytokines were quantified in cervicovaginal lavages. Potential sociodemographic, behavioral, and clinical correlates were also evaluated.

Results

Three hundred thirteen samples from 230 women were available for analysis. Five VMB clusters were identified: one cluster each dominated by Lactobacillus crispatus (KRST-I) and L. iners (KRST-II), and three clusters not dominated by a single species but containing multiple (facultative) anaerobes (KRST-III/IV/V). Women in clusters KRST-I and II had lower mean concentrations of interleukin (IL)-1α (p < 0.001) and Granulocyte Colony Stimulating Factor (G-CSF) (p = 0.01), but higher concentrations of interferon-γ-induced protein (IP-10) (p < 0.01) than women in clusters KRST-III/IV/V. A lower proportion of women in cluster KRST-I tested positive for bacterial sexually transmitted infections (STIs; ptrend = 0.07) and urinary tract infection (UTI; p = 0.06), and a higher proportion of women in clusters KRST-I and II had vaginal candidiasis (ptrend = 0.09), but these associations did not reach statistical significance. Women who reported unusual vaginal discharge were more likely to belong to clusters KRST-III/IV/V (p = 0.05).

Conclusion

Vaginal dysbiosis in African women was significantly associated with vaginal inflammation; the associations with increased prevalence of STIs and UTI, and decreased prevalence of vaginal candidiasis, should be confirmed in larger studies.
Appendix
Available only for authorised users
Literature
1.
go back to reference Redondo-Lopez V, Cook RL, Sobel JD. Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev Infect Dis. 1990;12:856–72.CrossRefPubMed Redondo-Lopez V, Cook RL, Sobel JD. Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev Infect Dis. 1990;12:856–72.CrossRefPubMed
2.
go back to reference Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983;74:14–22.CrossRefPubMed Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983;74:14–22.CrossRefPubMed
3.
go back to reference Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Jurriaans S, Ndayisaba GF, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 2014; doi:10.1038/ismej.2014.26. Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Jurriaans S, Ndayisaba GF, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 2014; doi:10.1038/ismej.2014.26.
4.
go back to reference Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis. 2003;37:319–25.CrossRefPubMed Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis. 2003;37:319–25.CrossRefPubMed
5.
go back to reference Watts DH, Fazzari M, Minkoff H, Hillier SL, Sha B, Glesby M, et al. Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women. J Infect Dis. 2005;191:1129–39.CrossRefPubMed Watts DH, Fazzari M, Minkoff H, Hillier SL, Sha B, Glesby M, et al. Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women. J Infect Dis. 2005;191:1129–39.CrossRefPubMed
6.
go back to reference van de Wijgert JH, Borgdorff H, Verhelst R, Crucitti T, Francis S, Verstraelen H, et al. The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One. 2014;9:e105998.CrossRefPubMedPubMedCentral van de Wijgert JH, Borgdorff H, Verhelst R, Crucitti T, Francis S, Verstraelen H, et al. The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One. 2014;9:e105998.CrossRefPubMedPubMedCentral
7.
go back to reference Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991;29:297–301.PubMedPubMedCentral Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991;29:297–301.PubMedPubMedCentral
8.
go back to reference Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108:4680–7.CrossRefPubMed Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108:4680–7.CrossRefPubMed
9.
go back to reference Fiscella K, Klebanoff MA. Are racial differences in vaginal pH explained by vaginal flora? Am J Obstet Gynecol. 2004;191:747–50.CrossRefPubMed Fiscella K, Klebanoff MA. Are racial differences in vaginal pH explained by vaginal flora? Am J Obstet Gynecol. 2004;191:747–50.CrossRefPubMed
10.
go back to reference Zhou X, Hansmann MA, Davis CC, Suzuki H, Brown CJ, Schütte U, et al. The vaginal bacterial communities of Japanese women resemble those of women in other racial groups. FEMS Immunol Med Microbiol. 2010;58:169–81.CrossRefPubMed Zhou X, Hansmann MA, Davis CC, Suzuki H, Brown CJ, Schütte U, et al. The vaginal bacterial communities of Japanese women resemble those of women in other racial groups. FEMS Immunol Med Microbiol. 2010;58:169–81.CrossRefPubMed
11.
go back to reference van de Wijgert J, Shattock R. Vaginal microbicides: moving ahead after an unexpected setback. Editorial review. AIDS. 2007;21:2369–76.CrossRefPubMed van de Wijgert J, Shattock R. Vaginal microbicides: moving ahead after an unexpected setback. Editorial review. AIDS. 2007;21:2369–76.CrossRefPubMed
12.
go back to reference Jespers V, Millwood IY, Poynten IM, Van Damme L, Kaldor JM. The evolving design and methods for trials evaluating the safety and candidate vaginal microbicides: a systematic review. Sex Transm Dis. 2013;40:729–36.CrossRefPubMed Jespers V, Millwood IY, Poynten IM, Van Damme L, Kaldor JM. The evolving design and methods for trials evaluating the safety and candidate vaginal microbicides: a systematic review. Sex Transm Dis. 2013;40:729–36.CrossRefPubMed
13.
go back to reference Fichorova RN, Tucker LD, Anderson DJ. The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. J Infect Dis. 2001;184:418–28.CrossRefPubMed Fichorova RN, Tucker LD, Anderson DJ. The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. J Infect Dis. 2001;184:418–28.CrossRefPubMed
14.
go back to reference Malonza IM, Mirembe F, Nakabiito C, Odusoga LO, Osinupebi OA, Hazari K, et al. Expanded phase I safety and acceptability study of 6% cellulose sulfate vaginal gel. AIDS. 2005;19:2157–63.CrossRefPubMed Malonza IM, Mirembe F, Nakabiito C, Odusoga LO, Osinupebi OA, Hazari K, et al. Expanded phase I safety and acceptability study of 6% cellulose sulfate vaginal gel. AIDS. 2005;19:2157–63.CrossRefPubMed
15.
go back to reference Doh AS, Ngoh N, Roddy R, Lai JJ, Linton K, Mauck C. Safety and acceptability of 6% cellulose sulfate vaginal gel applied four times per day for 14 days. Contraception. 2007;76:245–9.CrossRefPubMed Doh AS, Ngoh N, Roddy R, Lai JJ, Linton K, Mauck C. Safety and acceptability of 6% cellulose sulfate vaginal gel applied four times per day for 14 days. Contraception. 2007;76:245–9.CrossRefPubMed
16.
go back to reference Jespers V, Crucitti T, Menten J, Verhelst R, Mwaura M, Mandaliya K, et al. Prevalence and correlates of bacterial vaginosis in different subpopulations of women in sub-Saharan Africa: a cross-sectional study. PLoS One. 2014;9:e109670.CrossRefPubMedPubMedCentral Jespers V, Crucitti T, Menten J, Verhelst R, Mwaura M, Mandaliya K, et al. Prevalence and correlates of bacterial vaginosis in different subpopulations of women in sub-Saharan Africa: a cross-sectional study. PLoS One. 2014;9:e109670.CrossRefPubMedPubMedCentral
17.
go back to reference Francis SC, Baisley K, Hou Y, Herrera C, Andreasen A, Watson-Jones D, et al. Expression of soluble immune proteins in the female genital tract: Background variation among women at high risk for HIV in Tanzania. Abstract A-641-0263-09932, 20th International AIDS Conference, Melbourne, Australia. Francis SC, Baisley K, Hou Y, Herrera C, Andreasen A, Watson-Jones D, et al. Expression of soluble immune proteins in the female genital tract: Background variation among women at high risk for HIV in Tanzania. Abstract A-641-0263-09932, 20th International AIDS Conference, Melbourne, Australia.
18.
go back to reference Kapiga SH, Ewings FM, Ao T, Chilongani J, Mongi A, Baisley K, et al. The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania. PLoS One. 2013;8:e68825.CrossRefPubMedPubMedCentral Kapiga SH, Ewings FM, Ao T, Chilongani J, Mongi A, Baisley K, et al. The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania. PLoS One. 2013;8:e68825.CrossRefPubMedPubMedCentral
19.
go back to reference Kyongo JK, Crucitti T, Menten J, Hardy L, Cools P, Michiels J, et al. Genital tract immunological markers in Sub-Saharan African women with relevance to HIV risk and prevention. Clin Vaccine Immunol, in press. Kyongo JK, Crucitti T, Menten J, Hardy L, Cools P, Michiels J, et al. Genital tract immunological markers in Sub-Saharan African women with relevance to HIV risk and prevention. Clin Vaccine Immunol, in press.
20.
go back to reference Biancotto A, Grivel JC, Iqlehart SJ, Vanpouille C, Lisco A, Sieg SE, et al. Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood. 2007;109:4272–9.CrossRefPubMedPubMedCentral Biancotto A, Grivel JC, Iqlehart SJ, Vanpouille C, Lisco A, Sieg SE, et al. Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood. 2007;109:4272–9.CrossRefPubMedPubMedCentral
21.
go back to reference Fischetti L, Barry SM, Hope TJ, Shattock RJ. HIV-1 infection of human penile explant tissue and protection by candidate microbicides. AIDS. 2009;23:319–28.CrossRefPubMedPubMedCentral Fischetti L, Barry SM, Hope TJ, Shattock RJ. HIV-1 infection of human penile explant tissue and protection by candidate microbicides. AIDS. 2009;23:319–28.CrossRefPubMedPubMedCentral
22.
go back to reference Dols JA, Reid G, Kort R, Schuren FH, Tempelman H, Bontekoe TR, et al. PCR-based identification of eight Lactobacillus species and 18 hr-HPV genotypes in fixed cervical samples of South African women at risk of HIV and BV. Diagn Cytopathol. 2012;40:472–7.CrossRefPubMed Dols JA, Reid G, Kort R, Schuren FH, Tempelman H, Bontekoe TR, et al. PCR-based identification of eight Lactobacillus species and 18 hr-HPV genotypes in fixed cervical samples of South African women at risk of HIV and BV. Diagn Cytopathol. 2012;40:472–7.CrossRefPubMed
23.
go back to reference Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353:1899–911.CrossRefPubMed Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353:1899–911.CrossRefPubMed
24.
25.
go back to reference Tsivtsivadze E, Borgdorff H, van de Wijgert JHHM, Schuren FHJ, Verhelst R, Heskes T. Neighborhood co-regularized multi-veiw spectral clustering of microbiome data. Nanjing: Proceedings of 2nd workshop on partially supervised learning; 2013. Tsivtsivadze E, Borgdorff H, van de Wijgert JHHM, Schuren FHJ, Verhelst R, Heskes T. Neighborhood co-regularized multi-veiw spectral clustering of microbiome data. Nanjing: Proceedings of 2nd workshop on partially supervised learning; 2013.
26.
go back to reference Marzorati M, Maignien L, Verhelst A, Luta G, Sinnott R, Kerckhof FM, et al. Barcoded pyrosequencing analysis of the microbial community in a simulator of the human gastrointestinal tract showed a colon region-specific microbiota modulation for two plant-derived polysaccharide blends. Antonie Van Leeuwenhoek. 2013;103:409–20.CrossRefPubMed Marzorati M, Maignien L, Verhelst A, Luta G, Sinnott R, Kerckhof FM, et al. Barcoded pyrosequencing analysis of the microbial community in a simulator of the human gastrointestinal tract showed a colon region-specific microbiota modulation for two plant-derived polysaccharide blends. Antonie Van Leeuwenhoek. 2013;103:409–20.CrossRefPubMed
27.
go back to reference Shannon CE. A mathematical theory of communication. Bell Syst Tech J. 1948;27:379–423.CrossRef Shannon CE. A mathematical theory of communication. Bell Syst Tech J. 1948;27:379–423.CrossRef
28.
go back to reference Jespers V, Menten J, Smet H, Poradosu S, Abdellati S, Verhelst R, et al. Quantification of bacterial species of the vaginal microbiome in different groups of women, using nucleic acid amplification tests. BMC Microbiol. 2012;12. doi: 10.1186/1471-2180-12-83. Jespers V, Menten J, Smet H, Poradosu S, Abdellati S, Verhelst R, et al. Quantification of bacterial species of the vaginal microbiome in different groups of women, using nucleic acid amplification tests. BMC Microbiol. 2012;12. doi: 10.1186/1471-2180-12-83.
29.
30.
go back to reference Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis. 2014;209:1989–99.CrossRefPubMed Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis. 2014;209:1989–99.CrossRefPubMed
31.
go back to reference van de Wijgert JH, Verwijs MC, Turner AN, Morrison CS. Hormonal contraception decreases bacterial vaginosis but oral contraception may increase candidiasis: implications for HIV transmission. AIDS. 2013;27:2141–53.CrossRefPubMed van de Wijgert JH, Verwijs MC, Turner AN, Morrison CS. Hormonal contraception decreases bacterial vaginosis but oral contraception may increase candidiasis: implications for HIV transmission. AIDS. 2013;27:2141–53.CrossRefPubMed
32.
go back to reference Anderson BL, Mendez-Figueroa H, Dahlke JD, Raker C, Hillier SL, Cu-Uvin S. Pregnancy-induced changes in immune protection of the genital tract: defining normal. Am J Obstet Gynecol. 2013;208:321–9.PubMedPubMedCentral Anderson BL, Mendez-Figueroa H, Dahlke JD, Raker C, Hillier SL, Cu-Uvin S. Pregnancy-induced changes in immune protection of the genital tract: defining normal. Am J Obstet Gynecol. 2013;208:321–9.PubMedPubMedCentral
33.
go back to reference Low N, Chersich MF, Schmidlin K, Egger M, Francis SC, van de Wijgert JH. Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis. PLoS Med. 2011;8:e1000416. doi:10.1371/journal.pmed.1000416.CrossRefPubMedPubMedCentral Low N, Chersich MF, Schmidlin K, Egger M, Francis SC, van de Wijgert JH. Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis. PLoS Med. 2011;8:e1000416. doi:10.1371/journal.pmed.1000416.CrossRefPubMedPubMedCentral
34.
go back to reference Sha BE, Zariffard MR, Wang QJ, Chen HY, Bremer J, Cohen MH, et al. Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis. J Infect Dis. 2005;191:25–32.CrossRefPubMed Sha BE, Zariffard MR, Wang QJ, Chen HY, Bremer J, Cohen MH, et al. Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis. J Infect Dis. 2005;191:25–32.CrossRefPubMed
35.
go back to reference Spear GT, Sikaroodi M, Zariffard MR, Landay AL, French AL, Gillevet PM. Comparison of the diversity of the vaginal microbiota in HIV-infected and HIV-uninfected women with or without bacterial vaginosis. J Infect Dis. 2008;198:1131–40.CrossRefPubMedPubMedCentral Spear GT, Sikaroodi M, Zariffard MR, Landay AL, French AL, Gillevet PM. Comparison of the diversity of the vaginal microbiota in HIV-infected and HIV-uninfected women with or without bacterial vaginosis. J Infect Dis. 2008;198:1131–40.CrossRefPubMedPubMedCentral
36.
go back to reference Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11:244.CrossRefPubMedPubMedCentral Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11:244.CrossRefPubMedPubMedCentral
37.
go back to reference Fichorova RN, Richardson-Harman N, Alfano M, Belec L, Carbonneil C, Chen S, et al. Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study. Anal Chem. 2008;80:4741–51.CrossRefPubMedPubMedCentral Fichorova RN, Richardson-Harman N, Alfano M, Belec L, Carbonneil C, Chen S, et al. Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study. Anal Chem. 2008;80:4741–51.CrossRefPubMedPubMedCentral
Metadata
Title
Correlates of the molecular vaginal microbiota composition of African women
Authors
Raju Gautam
Hanneke Borgdorff
Vicky Jespers
Suzanna C Francis
Rita Verhelst
Mary Mwaura
Sinead Delany-Moretlwe
Gilles Ndayisaba
Jordan K Kyongo
Liselotte Hardy
Joris Menten
Tania Crucitti
Evgeni Tsivtsivadze
Frank Schuren
Janneke HHM van de Wijgert
for the Vaginal Biomarkers Study Group
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2015
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-015-0831-1

Other articles of this Issue 1/2015

BMC Infectious Diseases 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.