Vaginal microbiome: rethinking health and disease.

Vaginal microbiota form a mutually beneficial relationship with their host and have a major impact on health and disease. In recent years our understanding of vaginal bacterial community composition and structure has significantly broadened as a result of investigators using cultivation-independent methods based on the analysis of 16S ribosomal RNA (rRNA) gene sequences. In asymptomatic, otherwise healthy women, several kinds of vaginal microbiota exist, the majority often dominated by species of Lactobacillus, while others are composed of a diverse array of anaerobic microorganisms. Bacterial vaginosis is the most common vaginal condition and is vaguely characterized as the disruption of the equilibrium of the normal vaginal microbiota. A better understanding of normal and healthy vaginal ecosystems that is based on their true function and not simply on their composition would help better define health and further improve disease diagnostics as well as the development of more personalized regimens to promote health and treat diseases.

[1]  J. Marrazzo Reply to Forney et al. , 2006 .

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

[3]  R. Ness,et al.  Can known risk factors explain racial differences in the occurrence of bacterial vaginosis? , 2003, Journal of the National Medical Association.

[4]  D. Scharfstein,et al.  The effect of vaginal douching cessation on bacterial vaginosis: a pilot study. , 2008, American journal of obstetrics and gynecology.

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

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

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

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

[9]  J. Russell,et al.  The effects of fermentation acids on bacterial growth. , 1998, Advances in microbial physiology.

[10]  J. Sobel Is there a protective role for vaginal flora? , 1999, Current infectious disease reports.

[11]  M. Krohn,et al.  The relationship of hydrogen peroxide‐producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women , 1992, Obstetrics and gynecology.

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

[13]  T. Hope,et al.  Human Immunodeficiency Virus Type 1 Is Trapped by Acidic but Not by Neutralized Human Cervicovaginal Mucus , 2009, Journal of Virology.

[14]  W. Ledger,et al.  Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide. , 2011, FEMS immunology and medical microbiology.

[15]  S. Garland,et al.  High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. , 2006, The Journal of infectious diseases.

[16]  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.

[17]  J. Hogan,et al.  Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  C. Beck-Sague,et al.  Behaviors Associated with Neisseria gonorrhoeae and Chiamydia trachomatis: Cervical Infection Among Young Womena Attending Adolescent Clinics , 2000, Clinical pediatrics.

[19]  D. Hellberg,et al.  Bacterial vaginosis and smoking , 2000, International journal of STD & AIDS.

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

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

[22]  M. Graver,et al.  The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth , 2011, Annals of Clinical Microbiology and Antimicrobials.

[23]  P. Bork,et al.  Enterotypes of the human gut microbiome , 2011, Nature.

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

[25]  Jason A. Papin,et al.  Applications of genome-scale metabolic reconstructions , 2009, Molecular systems biology.

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

[27]  J. Fortenberry,et al.  Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis , 2004, BMC infectious diseases.

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

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

[30]  G. Doncel,et al.  Novel Vaginal Microflora Colonization Model Providing New Insight into Microbicide Mechanism of Action , 2011, mBio.

[31]  R. Ness,et al.  Condom Use and its Association With Bacterial Vaginosis and Bacterial Vaginosis-Associated Vaginal Microflora , 2007, Epidemiology.

[32]  M. S. St. Louis,et al.  A public health approach to adverse outcomes of pregnancy associated with bacterial vaginosis , 1999, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[33]  M. Chikindas,et al.  NATURAL ANTIMICROBIALS AND THEIR ROLE IN VAGINAL HEALTH: A SHORT REVIEW. , 2008, International journal of probiotics & prebiotics.

[34]  Jacques Ravel,et al.  Rapid fluctuation of the vaginal microbiota measured by Gram stain analysis , 2010, Sexually Transmitted Infections.

[35]  H. Ochman,et al.  Evolutionary dynamics of full genome content in Escherichia coli , 2000, The EMBO journal.

[36]  E. R. Kashket Bioenergetics of lactic acid bacteria: cytoplasmic pH and osmotolerance , 1987 .

[37]  K. Schleifer,et al.  Phylogenetic identification and in situ detection of individual microbial cells without cultivation. , 1995, Microbiological reviews.

[38]  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.

[39]  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.

[40]  J. Peipert,et al.  Screening for bacterial vaginosis in pregnancy. , 2001, American journal of preventive medicine.

[41]  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.

[42]  P. Larsson Treatment of Bacterial Vaginosis , 1992, International journal of STD & AIDS.

[43]  Sharon I. Greenblum,et al.  Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease , 2011, Proceedings of the National Academy of Sciences.

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

[45]  S. Batzoglou,et al.  Bacterial flora-typing with targeted, chip-based Pyrosequencing , 2007, BMC Microbiology.

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

[47]  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.

[48]  F. Aydın,et al.  Antimicrobial Activity and Characteristics of Bacteriocins Produced by Vaginal Lactobacilli , 2003 .

[49]  A. Pisabarro,et al.  Classification and mode of action of membrane-active bacteriocins produced by gram-positive bacteria , 2001, International microbiology : the official journal of the Spanish Society for Microbiology.

[50]  N. Sewankambo,et al.  HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis , 1997, The Lancet.

[51]  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.

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

[53]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[54]  E. Bosmans,et al.  Pathogenesis of abnormal vaginal bacterial flora. , 2000, American journal of obstetrics and gynecology.

[55]  R. Nguti,et al.  Infectious correlates of HIV-1 shedding in the female upper and lower genital tracts , 2007, AIDS.

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

[57]  P. Nyirjesy,et al.  Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. , 2006, American journal of obstetrics and gynecology.

[58]  Tom M. Conrad,et al.  Omic data from evolved E. coli are consistent with computed optimal growth from genome-scale models , 2010, Molecular systems biology.

[59]  M. Collins,et al.  Characterization of a novel Atopobium isolate from the human vagina: description of Atopobium vaginae sp. nov. , 1999, International journal of systematic bacteriology.

[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]  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.

[62]  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.

[63]  T. D. Read,et al.  Role of Mobile DNA in the Evolution of Vancomycin-Resistant Enterococcus faecalis , 2003, Science.

[64]  E. Thom,et al.  The preterm prediction study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. , 1995, American journal of obstetrics and gynecology.

[65]  L. Bakken Separation and Purification of Bacteria from Soil , 1985, Applied and environmental 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]  J. Sobel,et al.  Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. , 1993, The Journal of infectious diseases.

[68]  J. Schwebke,et al.  The Use of Sequential Self‐Obtained Vaginal Smears for Detecting Changes in the Vaginal Flora , 1997, Sexually transmitted diseases.

[69]  D. Taylor-Robinson,et al.  A longitudinal study of the vaginal flora over a menstrual cycle , 1997, International journal of STD & AIDS.

[70]  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.

[71]  M A Krohn,et al.  The normal vaginal flora, H2O2-producing lactobacilli, and bacterial vaginosis in pregnant women. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[72]  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.

[73]  H. Alakomi,et al.  Lactic Acid Permeabilizes Gram-Negative Bacteria by Disrupting the Outer Membrane , 2000, Applied and Environmental Microbiology.

[74]  A. Stapleton,et al.  Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections. , 1998, The Journal of infectious diseases.

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

[76]  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.

[77]  Meng-Yao Liu,et al.  Genome sequence of a serotype M3 strain of group A Streptococcus: Phage-encoded toxins, the high-virulence phenotype, and clone emergence , 2002, Proceedings of the National Academy of Sciences of the United States of America.

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

[79]  Rw Jack,et al.  Bacteriocins of grampositive bacteria , 1995 .

[80]  D. Scharfstein,et al.  A longitudinal study of vaginal douching and bacterial vaginosis--a marginal structural modeling analysis. , 2008, American journal of epidemiology.

[81]  Susan M. Huse,et al.  24. Microbial Diversity in the Deep Sea and the Underexplored “Rare Biosphere” , 2011 .

[82]  K. Holmes,et al.  Independent associations of bacterial vaginosis and Chlamydia trachomatis infection with adverse pregnancy outcome. , 1986, JAMA.

[83]  A. Ugwumadu,et al.  Sex, thrush and bacterial vaginosis , 1997, International journal of STD & AIDS.

[84]  J. Wilson,et al.  Bacterial vaginal flora in relation to changing oestrogen levels , 2007, International journal of STD & AIDS.

[85]  D. Taylor-Robinson,et al.  Comparison of Gram‐stained smears prepared from blind vaginal swabs with those obtained at speculum examination for the assessment of vaginal flora , 1996, British journal of obstetrics and gynaecology.

[86]  P. Reeves,et al.  Intraspecies variation in bacterial genomes: the need for a species genome concept. , 2000, Trends in microbiology.

[87]  P. Dyson,et al.  Pulsed-field gel electrophoresis of Streptomyces lividans DNA. , 1993, Trends in genetics : TIG.

[88]  Zaid Abdo,et al.  Temporal Dynamics of the Human Vaginal Microbiota , 2012, Science Translational Medicine.

[89]  S. Lynch,et al.  The potential for probiotic manipulation of the gastrointestinal microbiome. , 2012, Current opinion in biotechnology.

[90]  K. Nelson,et al.  Bacterial vaginosis and HIV seroprevalence among female commercial sex workers in Chiang Mai, Thailand , 1995, AIDS.

[91]  J. Tagg,et al.  Copyright � 1995, American Society for Microbiology Bacteriocins of Gram-Positive Bacteria , 1995 .

[92]  J. H. van de Wijgert,et al.  Intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in Zimbabwean women. , 2000, The Journal of infectious diseases.

[93]  D. Relman,et al.  An ecological and evolutionary perspective on human–microbe mutualism and disease , 2007, Nature.

[94]  D. Raoult,et al.  Molecular quantification of Gardnerella vaginalis and Atopobium vaginae loads to predict bacterial vaginosis. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[95]  R. Goldenberg,et al.  Sexually transmitted diseases and adverse outcomes of pregnancy. , 1997, Clinics in perinatology.

[96]  Jun Zhang,et al.  Vulvovaginal Symptoms in Women With Bacterial Vaginosis , 2004, Obstetrics and gynecology.

[97]  Susan M. Huse,et al.  Microbial diversity in the deep sea and the underexplored “rare biosphere” , 2006, Proceedings of the National Academy of Sciences.

[98]  D. Relman,et al.  Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates , 1996, Clinical microbiology reviews.

[99]  K. Workowski,et al.  Sexually transmitted diseases treatment guidelines, 2006. , 2006, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[100]  David A. Wardle,et al.  Stability of ecosystem properties in response to above‐ground functional group richness and composition , 2000 .

[101]  R. Ley,et al.  Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine , 2006, Cell.

[102]  L. Øvreås,et al.  Microbial diversity and function in soil: from genes to ecosystems. , 2002, Current opinion in microbiology.

[103]  E. Mardis,et al.  An obesity-associated gut microbiome with increased capacity for energy harvest , 2006, Nature.

[104]  J. Sobel,et al.  Validity of the Vaginal Gram Stain for the Diagnosis of Bacterial Vaginosis , 1996, Obstetrics and gynecology.

[105]  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.

[106]  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.

[107]  James A Foster,et al.  The vaginal flora of healthy women is not always dominated by Lactobacillus species. , 2006, The Journal of infectious diseases.

[108]  Elaine Holmes,et al.  A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model , 2007, Molecular systems biology.

[109]  V. Hogan,et al.  Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant women: a synthesis of data. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[110]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

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

[112]  M. Zariffard,et al.  Bacterial vaginosis and human immunodeficiency virus infection , 2007, AIDS research and therapy.

[113]  L. Hooper,et al.  Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin , 2006, Science.

[114]  Lu Wang,et al.  The NIH Human Microbiome Project. , 2009, Genome research.

[115]  R. Knight,et al.  Evolution of Mammals and Their Gut Microbes , 2008, Science.

[116]  S. Mazmanian,et al.  An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System , 2005, Cell.

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

[118]  David A. Relman,et al.  'Til death do us part': coming to terms with symbiotic relationships , 2008, Nature Reviews Microbiology.

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

[120]  R. Ness,et al.  A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. , 2005, American journal of epidemiology.

[121]  L. Meyn,et al.  Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[122]  P. Turnbaugh,et al.  The core gut microbiome, energy balance and obesity , 2009, The Journal of physiology.

[123]  Prenatal microbiological risk factors associated with preterm birth , 1992, British journal of obstetrics and gynaecology.