Genomic Tools For Studying The Ecology Of The Human Vaginal Microflora

Summary

Principal Investigator: Jacques Ravel
Abstract: The normal vaginal microflora in healthy women of reproductive age plays a key role in preventing successful colonization by "undesirable" organisms including those responsible for bacterial vaginosis, yeast infections, sexually transmitted diseases and urinary tract infections. Our long-term goal is to develop an accurate understanding of the composition and ecology of the vagina microbial ecosystem in normal, healthy women as an essential prerequisite for comprehending how the normal microflora reduces the risk of acquiring these communicable diseases and for defining the factors determining disease susceptibility. The specific hypotheses are that 1. women's genetic backgrounds influence the composition of the vaginal microflora, 2. while vaginal community compositions markedly vary amongst women, the functional potential of a community is similar. Tools necessary to test these hypotheses will be developed and are addressed by these specific aims: 1. Conduct a comprehensive survey of the vaginal microflora in 400 women of different ethnic background using 16S rRNA gene sequencing analysis. We will correlate the community composition with genetic background, and provide the basis for Aim 2. 2. Develop a 16S rDNA-based molecular tool (molecular inversion probes) to rapidly and quantitatively measure the microbial species composition and abundance of a vaginal community. 3. Characterized the metabolic potential of the vaginal microflora of healthy women by community genomics. We will sequence the "community genome" of the five most predominant community types. Sequence data and analysis will be freely accessible through the web-based Vaginal Microbiome Database. 4. Develop the Vaginal Microbiome Expression GeneChip(c) array, a high density oligonucleotide microarray- based tool for functional genomic analyses of vaginal microbial communities. Using this tool we will assess community gene expression over the course of two months, while monitoring reproductive hormone levels. We view this work as analogous to the human genome project, in which initial sequence information provided a platform for decades of future work focused on all aspect of human health and disease. Similarly, these tools will be critical for the study and evaluation of women's health.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy
    Rebecca M Brotman
    From the 1Institute for Genome Sciences and 2Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Departments of 4Pediatrics and Neurovirology and 5Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, MD and 6Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD
    Menopause 21:450-8. 2014
  2. pmc Association between Trichomonas vaginalis and vaginal bacterial community composition among reproductive-age women
    Rebecca M Brotman
    Department of Epidemiology and Public Health, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Sex Transm Dis 39:807-12. 2012
  3. pmc Recent advances in understanding the microbiology of the female reproductive tract and the causes of premature birth
    Xia Zhou
    Initiative for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID 83844 3051, USA
    Infect Dis Obstet Gynecol 2010:737425. 2010
  4. pmc Vaginal microbiome: rethinking health and disease
    Bing Ma
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, 21201, USA
    Annu Rev Microbiol 66:371-89. 2012
  5. pmc Understanding vaginal microbiome complexity from an ecological perspective
    Roxana J Hickey
    Institute for Bioinformatics and Evolutionary Studies IBEST, University of Idaho, Moscow, ID, USA
    Transl Res 160:267-82. 2012
  6. pmc Comparison of storage conditions for human vaginal microbiome studies
    Guoyun Bai
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 7:e36934. 2012
  7. pmc Temporal dynamics of the human vaginal microbiota
    Pawel Gajer
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Sci Transl Med 4:132ra52. 2012
  8. pmc Evaluation of methods for the extraction and purification of DNA from the human microbiome
    Sanqing Yuan
    Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America
    PLoS ONE 7:e33865. 2012
  9. pmc Moving pictures of the human microbiome
    J Gregory Caporaso
    Department of Chemistry and Biochemistry, University of Colorado, 215 UCB, Boulder, CO 80309, USA
    Genome Biol 12:R50. 2011
  10. pmc Vaginal microbiome of reproductive-age women
    Jacques Ravel
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Proc Natl Acad Sci U S A 108:4680-7. 2011

Scientific Experts

  • Larry Forney
  • J Gregory Caporaso
  • Jacques Ravel
  • Rebecca M Brotman
  • Pawel Gajer
  • Zaid Abdo
  • Xia Zhou
  • Guoyun Bai
  • Bing Ma
  • Joyce Sakamoto
  • Roxana J Hickey
  • Sanqing Yuan
  • Doug Fadrosh
  • Michelle D Shardell
  • Michelle I Silver
  • Patti E Gravitt
  • Anne E Burke
  • Raphael P Viscidi
  • Kathryn Chang
  • Hongqiu Yang
  • Jane M Carlton
  • Melissa Nandy
  • Kevin Ault
  • Sara S K Koenig
  • Li Fu
  • Dora B Cohen
  • Zhanshan Sam Ma
  • Ligia Peralta
  • Melissa Conrad
  • May H Blanchard
  • Xue Zhong
  • L Latey Bradford
  • Ursel M E Schütte
  • Jacob D Pierson
  • Ursel Schüette
  • Sam Ma

Detail Information

Publications11

  1. pmc Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy
    Rebecca M Brotman
    From the 1Institute for Genome Sciences and 2Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Departments of 4Pediatrics and Neurovirology and 5Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, MD and 6Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD
    Menopause 21:450-8. 2014
    ..We sought to describe the composition of the vaginal microbiota in premenopausal, perimenopausal, and postmenopausal women and to explore the association between the microbiota and vulvovaginal atrophy (VVA)...
  2. pmc Association between Trichomonas vaginalis and vaginal bacterial community composition among reproductive-age women
    Rebecca M Brotman
    Department of Epidemiology and Public Health, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Sex Transm Dis 39:807-12. 2012
    ..We sought to evaluate the relationship between vaginal bacterial composition and Trichomonas vaginalis...
  3. pmc Recent advances in understanding the microbiology of the female reproductive tract and the causes of premature birth
    Xia Zhou
    Initiative for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID 83844 3051, USA
    Infect Dis Obstet Gynecol 2010:737425. 2010
    ..Further research is needed to establish whether an ascending pathway from the vagina to the amniotic cavity enables the development of intrauterine infections...
  4. pmc Vaginal microbiome: rethinking health and disease
    Bing Ma
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, 21201, USA
    Annu Rev Microbiol 66:371-89. 2012
    ....
  5. pmc Understanding vaginal microbiome complexity from an ecological perspective
    Roxana J Hickey
    Institute for Bioinformatics and Evolutionary Studies IBEST, University of Idaho, Moscow, ID, USA
    Transl Res 160:267-82. 2012
    ....
  6. pmc Comparison of storage conditions for human vaginal microbiome studies
    Guoyun Bai
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 7:e36934. 2012
    ..We evaluated the effect of two common storage conditions used in clinical trials on the bacterial and metabolite composition of the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing and (1)H-NMR analyses...
  7. pmc Temporal dynamics of the human vaginal microbiota
    Pawel Gajer
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Sci Transl Med 4:132ra52. 2012
    ..The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis...
  8. pmc Evaluation of methods for the extraction and purification of DNA from the human microbiome
    Sanqing Yuan
    Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America
    PLoS ONE 7:e33865. 2012
    ..A fundamental challenge in using these approaches has been to isolate DNA that is representative of the microbial community sampled...
  9. pmc Moving pictures of the human microbiome
    J Gregory Caporaso
    Department of Chemistry and Biochemistry, University of Colorado, 215 UCB, Boulder, CO 80309, USA
    Genome Biol 12:R50. 2011
    ..Here, we present the largest human microbiota time series analysis to date, covering two individuals at four body sites over 396 timepoints...
  10. pmc Vaginal microbiome of reproductive-age women
    Jacques Ravel
    Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Proc Natl Acad Sci U S A 108:4680-7. 2011
    ....
  11. pmc Comparison of self-collected and physician-collected vaginal swabs for microbiome analysis
    Larry J Forney
    Department fo Biological Sciences, University of Idaho, Moscow, ID 83844 3051, USA
    J Clin Microbiol 48:1741-8. 2010
    ..These findings enable large-scale, field-based studies of the vaginal microbiome...