Understanding vaginal microbiome complexity from an ecological perspective.

The various microbiota normally associated with the human body have an important influence on human development, physiology, immunity, and nutrition. This is certainly true for the vagina wherein communities of mutualistic bacteria constitute the first line of defense for the host by excluding invasive, nonindigenous organisms that may cause disease. In recent years much has been learned about the bacterial species composition of these communities and how they differ between individuals of different ages and ethnicities. A deeper understanding of their origins and the interrelationships of constituent species is needed to understand how and why they change over time or in response to changes in the host environment. Moreover, there are few unifying theories to explain the ecological dynamics of vaginal ecosystems as they respond to disturbances caused by menses and human activities such as intercourse, douching, and other habits and practices. This fundamental knowledge is needed to diagnose and assess risk to disease. Here we summarize what is known about the species composition, structure, and function of bacterial communities in the human vagina and the applicability of ecological models of community structure and function to understanding the dynamics of this and other ecosystems that comprise the human microbiome.

[1]  Philip Hugenholtz,et al.  Impact of Culture-Independent Studies on the Emerging Phylogenetic View of Bacterial Diversity , 1998, Journal of bacteriology.

[2]  K. Whaley,et al.  Boskey, E.R., Cone, R.A., Whaley, K.J. & Moench, T.R. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum. Reprod. 16, 1809-1813 , 2001 .

[3]  M. Millar,et al.  Identification and H2O2 Production of Vaginal Lactobacilli from Pregnant Women at High Risk of Preterm Birth and Relation with Outcome , 2004, Journal of Clinical Microbiology.

[4]  K. Holmes,et al.  Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. , 1996, The Journal of infectious diseases.

[5]  J. Schwebke,et al.  Correlation of behaviors with microbiological changes in vaginal flora. , 1999, The Journal of infectious diseases.

[6]  J. Sobel,et al.  Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. , 1990, Reviews of infectious diseases.

[7]  O. Kandler,et al.  Heterogeneity of the species Lactobacillus acidophilus (Moro) Hansen and Moquot as revealed by biochemical characteristics and DNA-DNA hybridisation. , 1980 .

[8]  R. Lillis,et al.  Quantitative PCR Assessments of Bacterial Species in Women with and without Bacterial Vaginosis , 2010, Journal of Clinical Microbiology.

[9]  K. Whaley,et al.  Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. , 2001, Human reproduction.

[10]  S. Hillier,et al.  The vaginal microbial ecosystem and resistance to HIV. , 1998, AIDS research and human retroviruses.

[11]  J. Jacobson,et al.  Bacterial flora of the vagina during the menstrual cycle: findings in users of tampons, napkins, and sea sponges. , 1982, Annals of internal medicine.

[12]  J. Sobel,et al.  Dynamics of the Vaginal Ecosystem—Hormonal Influences , 2010 .

[13]  V. Rauh,et al.  Stress, bacterial vaginosis, and the role of immune processes , 2006, Current infectious disease reports.

[14]  David N. Fredricks,et al.  The Human Vaginal Bacterial Biota and Bacterial Vaginosis , 2009, Interdisciplinary perspectives on infectious diseases.

[15]  J. Kendrick,et al.  The Prevalence of Bacterial Vaginosis in the United States, 2001–2004; Associations With Symptoms, Sexual Behaviors, and Reproductive Health , 2007, Sexually transmitted diseases.

[16]  R. Desmond,et al.  Predictors of Bacterial Vaginosis in Adolescent Women Who Douche , 2004, Sexually transmitted diseases.

[17]  A. Onderdonk,et al.  Evidence for a commensal, symbiotic relationship between Gardnerella vaginalis and Prevotella bivia involving ammonia: potential significance for bacterial vaginosis. , 1997, The Journal of infectious diseases.

[18]  J. Sobel What's new in bacterial vaginosis and trichomoniasis? , 2005, Infectious disease clinics of North America.

[19]  A. Bruce,et al.  Hydrogen peroxide production by Lactobacillus species: correlation with susceptibility to the spermicidal compound nonoxynol-9. , 1992, The Journal of infectious diseases.

[20]  J. Marrazzo,et al.  Molecular identification of bacteria associated with bacterial vaginosis. , 2005, The New England journal of medicine.

[21]  R. Gibbs,et al.  Evidence relating bacterial vaginosis to intraamniotic infection. , 1989, American journal of obstetrics and gynecology.

[22]  G. Reid,et al.  Improved Understanding of the Bacterial Vaginal Microbiota of Women before and after Probiotic Instillation , 2003, Applied and Environmental Microbiology.

[23]  B. Larsen,et al.  Understanding the bacterial flora of the female genital tract. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  A. Nicoll,et al.  Bacterial vaginosis: a public health review , 2001, BJOG : an international journal of obstetrics and gynaecology.

[25]  R. Sweet,et al.  Role of bacterial vaginosis in pelvic inflammatory disease. , 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  S. Witkin,et al.  Contemporary perspectives on vaginal pH and lactobacilli. , 2011, American journal of obstetrics and gynecology.

[27]  P. Hay,et al.  High prevalence of bacterial vaginosis in adolescent girls in a tropical area of Ecuador , 2010, BJOG : an international journal of obstetrics and gynaecology.

[28]  C. Davis,et al.  Characterization of Microbial Communities Found in the Human Vagina by Analysis of Terminal Restriction Fragment Length Polymorphisms of 16S rRNA Genes , 2005, Applied and Environmental Microbiology.

[29]  H. Ward,et al.  Effect on normal vaginal flora of three intravaginal microbicidal agents potentially active against human immunodeficiency virus type 1. , 1998, The Journal of infectious diseases.

[30]  J. Faith,et al.  Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice , 2011, Proceedings of the National Academy of Sciences.

[31]  D. Orr,et al.  Vaginal Lactobacilli in Adolescents: Presence and Relationship to Local and Systemic Immunity, and to Bacterial Vaginosis , 2004, Sexually transmitted diseases.

[32]  K. Holmes,et al.  Nonspecific vaginitis: Diagnostic criteria and microbial and epidemiologic associations , 1983 .

[33]  P. Gajer,et al.  Vaginal microbiome of reproductive-age women , 2010, Proceedings of the National Academy of Sciences.

[34]  E. Purdom,et al.  Diversity of the Human Intestinal Microbial Flora , 2005, Science.

[35]  S. Ledru,et al.  Etiologic Study of Genitourinary Infections in Women of Childbearing Age in Bobo‐Dioulasso, Burkina Faso, 1992 , 1996, Sexually transmitted diseases.

[36]  R. Hobbs,et al.  Disturbance, Diversity, and Invasion: Implications for Conservation , 1992 .

[37]  N. Sakuragi,et al.  Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women , 2007, BMC infectious diseases.

[38]  M. Collins,et al.  Phenotypic and phylogenetic characterization of a novel Lactobacillus species from human sources: description of Lactobacillus iners sp. nov. , 1999, International journal of systematic bacteriology.

[39]  R. Knight,et al.  The Human Microbiome Project , 2007, Nature.

[40]  S. Hillier,et al.  Effects of contraceptive method on the vaginal microbial flora: a prospective evaluation. , 2000, The Journal of infectious diseases.

[41]  J. Marrazzo,et al.  Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. , 2002, The Journal of infectious diseases.

[42]  S. Shott,et al.  Defense factors of vaginal lactobacilli. , 2001, American journal of obstetrics and gynecology.

[43]  M. Rogosa,et al.  Species differentiation of human vaginal lactobacilli. , 1960, Journal of general microbiology.

[44]  J. Dhar,et al.  What is normal vaginal flora? , 1997, British medical journal.

[45]  W. Crosby,et al.  Characterization of vaginal microflora of healthy, nonpregnant women by chaperonin-60 sequence-based methods. , 2005, American journal of obstetrics and gynecology.

[46]  J. Marrazzo,et al.  Targeted PCR for Detection of Vaginal Bacteria Associated with Bacterial Vaginosis , 2007, Journal of Clinical Microbiology.

[47]  L. Dicks,et al.  Evaluation of random amplified polymorphic DNA (RAPD)-PCR as a method to differentiate Lactobacillus acidophilus, Lactobacillus crispatus, Lactobacillus amylovorus, Lactobacillus gallinarum, Lactobacillus gasseri, and Lactobacillus johnsonii , 1995, Current Microbiology.

[48]  B. Kocić,et al.  Bacteriological findings of the vulvar swab specimens from girls with vulvovaginitis , 2005 .

[49]  P. Schlievert,et al.  In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses. , 2005, Journal of applied physiology.

[50]  M. Krohn,et al.  Factors associated with absence of H2O2-producing Lactobacillus among women with bacterial vaginosis. , 2005, The Journal of infectious diseases.

[51]  John L. Johnson,et al.  Taxonomy of the Lactobacillus acidophilus Group , 1980 .

[52]  A. Onderdonk,et al.  Quantitative assessment of vaginal microflora during use of tampons of various compositions , 1987, Applied and environmental microbiology.

[53]  R. Ness,et al.  Bacterial vaginosis and anaerobic bacteria are associated with endometritis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[54]  P. Hay Bacterial vaginosis and miscarriage , 2004, Current opinion in infectious diseases.

[55]  M. Krohn,et al.  Bacterial colonization of the vagina during pregnancy in four ethnic groups. , 1996, American journal of obstetrics and gynecology.

[56]  S. Giovannoni,et al.  High-Throughput Methods for Culturing Microorganisms in Very-Low-Nutrient Media Yield Diverse New Marine Isolates , 2002, Applied and Environmental Microbiology.

[57]  C. Boyer,et al.  Bacterial Vaginosis in Sexually Experienced and Non–Sexually Experienced Young Women Entering the Military , 2003, Obstetrics and gynecology.

[58]  M. Vaneechoutte,et al.  Culture-independent analysis of vaginal microflora: the unrecognized association of Atopobium vaginae with bacterial vaginosis. , 2004, American journal of obstetrics and gynecology.

[59]  M. Wilks,et al.  Quantitative bacteriology of the vaginal flora during the menstrual cycle. , 1987, Journal of medical microbiology.

[60]  T. Ball,et al.  Pyrosequencing of the Chaperonin-60 Universal Target as a Tool for Determining Microbial Community Composition , 2009, Applied and Environmental Microbiology.

[61]  G. Schmid,et al.  Bacterial vaginosis and HIV infection , 2000, Sexually transmitted infections.

[62]  M. Collins,et al.  Comparative sequence analyses of the 16S rRNA genes of Lactobacillus minutus, Lactobacillus rimae and Streptococcus parvulus: proposal for the creation of a new genus Atopobium. , 1992, FEMS microbiology letters.

[63]  E. R. Carrington,et al.  Quantitative microflora of the vagina. , 1977, American journal of obstetrics and gynecology.

[64]  A species-specific PCR for Lactobacillus iners demonstrates a relative specificity of this species for vaginal colonization , 2008 .

[65]  S. Ahrné,et al.  Vaginal Lactobacillus Flora of Healthy Swedish Women , 2002, Journal of Clinical Microbiology.

[66]  M. Vaneechoutte,et al.  Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis , 2004, BMC Microbiology.

[67]  R. Cone,et al.  Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli , 2010, BMC infectious diseases.

[68]  H. Maibach,et al.  Lifetime changes in the vulva and vagina , 2005, Archives of Gynecology and Obstetrics.

[69]  J. Marrazzo,et al.  Temporal Variability of Human Vaginal Bacteria and Relationship with Bacterial Vaginosis , 2010, PloS one.

[70]  K. Holmes,et al.  Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis , 1989, Journal of clinical microbiology.

[71]  L. T. Angenent,et al.  Succession of microbial consortia in the developing infant gut microbiome , 2010, Proceedings of the National Academy of Sciences.

[72]  Alexandra Kaider,et al.  Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. , 2003, American journal of obstetrics and gynecology.

[73]  M. Krohn,et al.  Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[74]  A. Meier,et al.  Influence of the normal menstrual cycle on vaginal tissue, discharge, and microflora. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[75]  C. Sentman,et al.  Innate and adaptive immunity in female genital tract: cellular responses and interactions , 2005, Immunological reviews.

[76]  K. Whaley,et al.  Acid Production by Vaginal Flora In Vitro Is Consistent with the Rate and Extent of Vaginal Acidification , 1999, Infection and Immunity.

[77]  L. Bakken Separation and Purification of Bacteria from Soil , 1985, Applied and environmental microbiology.

[78]  Daniel B. DiGiulio,et al.  Development of the Human Infant Intestinal Microbiota , 2007, PLoS biology.

[79]  Yeonhee Lee,et al.  Analysis of vaginal lactic acid producing bacteria in healthy women. , 2007, Journal of microbiology.

[80]  D R Hoover,et al.  Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV , 1998, AIDS.

[81]  Elisabeth M Bik,et al.  Molecular analysis of the bacterial microbiota in the human stomach. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[82]  Mardge H. Cohen,et al.  Utility of Amsel Criteria, Nugent Score, and Quantitative PCR for Gardnerella vaginalis, Mycoplasma hominis, and Lactobacillus spp. for Diagnosis of Bacterial Vaginosis in Human Immunodeficiency Virus-Infected Women , 2005, Journal of Clinical Microbiology.

[83]  M. Burns,et al.  Microdroplet-Enabled Highly Parallel Co-Cultivation of Microbial Communities , 2011, PloS one.

[84]  T. Iannicelli,et al.  Prevalence of Bacterial Vaginosis and Vaginal Flora Changes in Peri- and Postmenopausal Women , 2002, Journal of Clinical Microbiology.

[85]  R. Galask,et al.  Effect of Estrogen Treatment on the Genital Tract Flora of Postmenopausal Women , 1982, Obstetrics and gynecology.

[86]  M. Krohn,et al.  Lower Genital Tract Infection and Endometritis: Insight Into Subclinical Pelvic Inflammatory Disease , 2002, Obstetrics and gynecology.

[87]  M. Hammerschlag,et al.  Microbiology of the vagina in children: normal and potentially pathogenic organisms. , 1978, Pediatrics.

[88]  Mohammed R. Islam,et al.  Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods. , 2004, Microbiology.

[89]  Kazumasa Fukuda,et al.  Influence of menstruation on the microbiota of healthy women's labia minora as analyzed using a 16S rRNA gene-based clone library method. , 2011, Japanese journal of infectious diseases.

[90]  J. Bartlett,et al.  Anaerobic microflora of the vagina in children. , 1978, American journal of obstetrics and gynecology.

[91]  S. Hillier,et al.  The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. , 1999, The Journal of infectious diseases.

[92]  Ursel M. E. Schütte,et al.  The vaginal bacterial communities of Japanese women resemble those of women in other racial groups. , 2010, FEMS immunology and medical microbiology.

[93]  Chris J. Williams,et al.  Bacterial populations in the vaginas of healthy adolescent women. , 2009, Journal of pediatric and adolescent gynecology.

[94]  K. McCann The diversity–stability debate , 2000, Nature.

[95]  J. Marrazzo,et al.  Relationship of Specific Vaginal Bacteria and Bacterial Vaginosis Treatment Failure in Women Who Have Sex with Women , 2008, Annals of Internal Medicine.

[96]  R. Knight,et al.  Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns , 2010, Proceedings of the National Academy of Sciences.

[97]  W. König,et al.  Rapid characterization of the normal and disturbed vaginal microbiota by application of 16S rRNA gene terminal RFLP fingerprinting. , 2007, Journal of medical microbiology.

[98]  M. Vaneechoutte,et al.  Bmc Microbiology , 2022 .

[99]  Adeeba Kamarulzaman,et al.  AIDS Res Hum Retroviruses , 2006 .

[100]  G. Donders Definition and classification of abnormal vaginal flora. , 2007, Best practice & research. Clinical obstetrics & gynaecology.

[101]  B. Jones,et al.  A study of the prevalence of hydrogen peroxide generating Lactobacilli in bacterial vaginosis: the determination of H2O2 concentrations generated, in vitro , by isolated strains and the levels found in vaginal secretions of women with and without infection. , 1998, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.

[102]  James M. Tanner,et al.  Variations in pattern of pubertal changes in girls. , 1969 .

[103]  T. P. Jackson,et al.  Race/ethnicity, vaginal flora patterns, and pH during pregnancy. , 1999, Sexually transmitted diseases.

[104]  H. Hayashi,et al.  Detection of potentially novel bacterial components of the human skin microbiota using culture-independent molecular profiling. , 2005, Journal of medical microbiology.

[105]  B. Walker Conserving Biological Diversity through Ecosystem Resilience , 1995 .

[106]  Zaid Abdo,et al.  Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women , 2007, The ISME Journal.

[107]  S. Thomas Döderlein's Bacillus: Lactobacillus Acidophilus , 1928 .

[108]  Anke Jentsch,et al.  The Search for Generality in Studies of Disturbance and Ecosystem Dynamics , 2001 .

[109]  S. Pimm The complexity and stability of ecosystems , 1984, Nature.

[110]  S. Giovannoni,et al.  Improvements of high-throughput culturing yielded novel SAR11 strains and other abundant marine bacteria from the Oregon coast and the Bermuda Atlantic Time Series study site , 2007, The ISME Journal.

[111]  Fabian M. Jaksic,et al.  Abuse and Misuse of the Term "Guild" in Ecological Studies , 1981 .

[112]  Ronald W. Davis,et al.  Microbes on the human vaginal epithelium , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[113]  J. Marrazzo,et al.  Distribution of genital Lactobacillus strains shared by female sex partners. , 2009, The Journal of infectious diseases.

[114]  M. Ferris,et al.  Cultivation-Independent Analysis of Changes in Bacterial Vaginosis Flora Following Metronidazole Treatment , 2007, Journal of Clinical Microbiology.

[115]  Safiyh Taghavi,et al.  Use of Single-Point Genome Signature Tags as a Universal Tagging Method for Microbial Genome Surveys , 2006, Applied and Environmental Microbiology.

[116]  A. Rutherford,et al.  Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study , 1999, BMJ.

[117]  Christina H. Park,et al.  Antimicrobial components of vaginal fluid. , 2002, American journal of obstetrics and gynecology.

[118]  L. Gunderson Ecological Resilience—In Theory and Application , 2000 .

[119]  R. Didham,et al.  Are invasive species the drivers of ecological change? , 2005, Trends in ecology & evolution.

[120]  Mary Frances Cotch,et al.  Association between Bacterial Vaginosis and Preterm Delivery of a Low-Birth-Weight Infant , 1995 .

[121]  R. Cone,et al.  In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide , 2011, BMC infectious diseases.

[122]  M. Krohn,et al.  Bacterial Vaginosis as a Risk Factor for Post- Cesarean Endometritis , 1990, Obstetrics and gynecology.

[123]  M A Krohn,et al.  Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation , 1991, Journal of clinical microbiology.

[124]  B. Chohan,et al.  Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. , 1999, The Journal of infectious diseases.

[125]  H. L. Gardner,et al.  Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. , 1955, American journal of obstetrics and gynecology.

[126]  M. Vaneechoutte,et al.  Quantitative determination by real-time PCR of four vaginal Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse relationship between L. gasseri and L. iners , 2007, BMC Microbiology.

[127]  Jianqian Tong,et al.  Preliminary characterization of vaginal microbiota in healthy Chinese women using cultivation‐independent methods , 2009, The journal of obstetrics and gynaecology research.

[128]  M. Vaneechoutte,et al.  Comparison between Gram stain and culture for the characterization of vaginal microflora: Definition of a distinct grade that resembles grade I microflora and revised categorization of grade I microflora , 2005, BMC Microbiology.

[129]  S. Klebanoff Effects of the spermicidal agent nonoxynol-9 on vaginal microbial flora. , 1992, The Journal of infectious diseases.

[130]  D. Taylor-Robinson,et al.  Relationship between hydrogen peroxide-producing strains of lactobacilli and vaginosis-associated bacterial species in pregnant women , 1997, European Journal of Clinical Microbiology and Infectious Diseases.

[131]  V. Rauh,et al.  Exposure to chronic stress and ethnic differences in rates of bacterial vaginosis among pregnant women. , 2002, American journal of obstetrics and gynecology.

[132]  O. Kiriwat,et al.  Accuracy of Nugent's score and each Amsel's criteria in the diagnosis of bacterial vaginosis. , 2004, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[133]  J. Jonasson,et al.  Identification of randomly selected colonies of lactobacilli from normal vaginal fluid by pyrosequencing of the 16S rDNA variable V1 and V3 regions , 2002, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[134]  A. Henderson,et al.  Identity and glycogen-fermenting ability of lactobacilli isolated from the vagina of pregnant women. , 1969, Journal of medical microbiology.

[135]  J. Klausner,et al.  Prevalence of bacterial vaginosis among young women in low-income populations of coastal Peru , 2007, International journal of STD & AIDS.

[136]  M. Klebanoff,et al.  The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort. , 2006, American journal of obstetrics and gynecology.

[137]  M. Delaney,et al.  Quantitative and Qualitative Effects of Douche Preparations on Vaginal Microflora , 1992, Obstetrics and gynecology.

[138]  J. Piper,et al.  Predictors of the vaginal microflora. , 2001, American journal of obstetrics and gynecology.

[139]  H. Dalton,et al.  Vaginal Flora in Postmenopausal Women: The Effect of Estrogen Replacement , 1993, Infectious diseases in obstetrics and gynecology.

[140]  K. Holmes,et al.  Diagnosis and clinical manifestations of bacterial vaginosis. , 1988, American journal of obstetrics and gynecology.

[141]  S. Hillier,et al.  Factors associated with acquisition of, or persistent colonization by, vaginal lactobacilli: role of hydrogen peroxide production. , 2001, The Journal of infectious diseases.

[142]  G. Reid,et al.  Lactobacillus Vaginal Microbiota of Women Attending a Reproductive Health Care Service in Benin City, Nigeria , 2006, Sexually transmitted diseases.

[143]  K. Schleifer,et al.  Phylogeny of the Genus Lactobacillus and Related Genera , 1995 .