Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases.

The vaginal microbiota has great significance in maintaining vaginal health and protecting the host from disease. Recent advances in molecular techniques and informatics allow researchers to explore microbial composition in detail and to compare the structure of vaginal microbial communities with behavior and health outcomes, particularly acquisition and transmission of sexually transmitted diseases (STDs) and poor birth outcomes. Vaginal flora have been found to cluster into a limited number of communities, although community structure is dynamic. Certain community types are more associated with poor reproductive outcomes and STDs; communities dominated by Lactobacillus species, particularly Lactobacillus crispatus, are most associated with vaginal health. Modifiable and nonmodifiable factors are strongly associated with community composition, including behavior, race or ethnicity, and hygiene. In this review, we describe the state of the science on the vaginal microbiome and its relationship to behavior, sexual health, and STDs, including determinants of the microbiome that go beyond an individual level.

[1]  M. Herbst-Kralovetz,et al.  Menopause and the vaginal microbiome. , 2016, Maturitas.

[2]  M. Klebanoff,et al.  Recent Biomarker-Confirmed Unprotected Vaginal Sex, But Not Self-reported Unprotected Sex, Is Associated With Recurrent Bacterial Vaginosis , 2016, Sexually transmitted diseases.

[3]  S. Philip,et al.  Home Screening for Bacterial Vaginosis to Prevent Sexually Transmitted Diseases. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  Amnon Amir,et al.  Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer , 2016, Nature Medicine.

[5]  S. Nakae,et al.  Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa , 2016, Proceedings of the National Academy of Sciences.

[6]  Michael L. Wilson,et al.  Social behavior shapes the chimpanzee pan-microbiome , 2016, Science Advances.

[7]  J. Hocking,et al.  Factors Associated with Bacterial Vaginosis among Women Who Have Sex with Women: A Systematic Review , 2015, PloS one.

[8]  H. Kiss,et al.  Role of Lactobacillus Species in the Intermediate Vaginal Flora in Early Pregnancy: A Retrospective Cohort Study , 2015, PloS one.

[9]  W. Catherino,et al.  Gynecologic health and disease in relation to the microbiome of the female reproductive tract. , 2015, Fertility and sterility.

[10]  J. K. Nicholson,et al.  Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity , 2015, Scientific Reports.

[11]  S. Witkin,et al.  Differential expression of lactic acid isomers, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase‐8 in vaginal fluid from women with vaginal disorders , 2015, BJOG : an international journal of obstetrics and gynaecology.

[12]  Samuel K. Lai,et al.  Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota , 2015, mBio.

[13]  Katherine H. Huang,et al.  Host genetic variation impacts microbiome composition across human body sites , 2015, Genome Biology.

[14]  D. Relman.  The Human Microbiome and the Future Practice of Medicine. , 2015, JAMA.

[15]  James Kinross,et al.  The gut microbiota and host health: a new clinical frontier , 2015, Gut.

[16]  C. Morrison,et al.  The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception , 2015, mBio.

[17]  M. Vaneechoutte,et al.  Unravelling the Bacterial Vaginosis-Associated Biofilm: A Multiplex Gardnerella vaginalis and Atopobium vaginae Fluorescence In Situ Hybridization Assay Using Peptide Nucleic Acid Probes , 2015, PloS one.

[18]  Christine L. Sun,et al.  Temporal and spatial variation of the human microbiota during pregnancy , 2015, Proceedings of the National Academy of Sciences.

[19]  R. Brotman,et al.  Making inroads into improving treatment of bacterial vaginosis – striving for long-term cure , 2015, BMC Infectious Diseases.

[20]  A. Hanlon,et al.  First Trimester Levels of BV-Associated Bacteria and Risk of Miscarriage Among Women Early in Pregnancy , 2015, Maternal and Child Health Journal.

[21]  M. Klebanoff,et al.  Risk of Bacterial Vaginosis Among Women With Herpes Simplex Virus Type 2 Infection: A Systematic Review and Meta-analysis. , 2015, The Journal of infectious diseases.

[22]  J. Ravel,et al.  Penile Microbiota and Female Partner Bacterial Vaginosis in Rakai, Uganda , 2015, mBio.

[23]  T. Bale,et al.  Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain. , 2015, Endocrinology.

[24]  R. Cone,et al.  Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis , 2015, Front. Physiol..

[25]  Daniel Raftery,et al.  Metabolic Signatures of Bacterial Vaginosis , 2015, mBio.

[26]  J. Hocking,et al.  Incident bacterial vaginosis (BV) in women who have sex with women is associated with behaviors that suggest sexual transmission of BV. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  L. Pascual,et al.  Bacteriocins and other bioactive substances of probiotic lactobacilli as biological weapons against Neisseria gonorrhoeae. , 2015, Pathogens and disease.

[28]  C. Kenyon,et al.  Sexual networks, HIV, race and bacterial vaginosis. , 2015, AIDS.

[29]  N. Angelopoulos,et al.  The vaginal microbiome during pregnancy and the postpartum period in a European population , 2015, Scientific Reports.

[30]  S. Delany-Moretlwe,et al.  The significance of Lactobacillus crispatus and L. vaginalis for vaginal health and the negative effect of recent sex: a cross-sectional descriptive study across groups of African women , 2015, BMC Infectious Diseases.

[31]  S. Delany-Moretlwe,et al.  Correlates of the molecular vaginal microbiota composition of African women , 2015, BMC Infectious Diseases.

[32]  M. Morris,et al.  The racial disparities in STI: Concurrency, STI prevalence, and heterogeneity in partner selection , 2015, Epidemics.

[33]  R. Cone.  Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIV. , 2014, The Journal of infectious diseases.

[34]  Jacques Ravel,et al.  Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. , 2014, The Journal of infectious diseases.

[35]  S. Delany-Moretlwe,et al.  Prevalence and Correlates of Bacterial Vaginosis in Different Sub-Populations of Women in Sub-Saharan Africa: A Cross-Sectional Study , 2014, PloS one.

[36]  Jennifer M. Fettweis,et al.  Differences in vaginal microbiome in African American women versus women of European ancestry. , 2014, Microbiology.

[37]  P. Gajer,et al.  Association between cigarette smoking and the vaginal microbiota: a pilot study , 2014, BMC Infectious Diseases.

[38]  Suzanna C. Francis,et al.  The Vaginal Microbiota: What Have We Learned after a Decade of Molecular Characterization? , 2014, PloS one.

[39]  M. McElrath,et al.  Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells. , 2014, The Journal of infectious diseases.

[40]  Mardge H. Cohen,et al.  Free Glycogen in Vaginal Fluids Is Associated with Lactobacillus Colonization and Low Vaginal pH , 2014, PloS one.

[41]  Y. Lo,et al.  Lactobacillus crispatus Dominant Vaginal Microbiome Is Associated with Inhibitory Activity of Female Genital Tract Secretions against Escherichia coli , 2014, PloS one.

[42]  M. Klebanoff,et al.  Bacterial Vaginosis and Season, a Proxy for Vitamin D Status , 2014, Sexually transmitted diseases.

[43]  Marc M. Baum,et al.  Cultivated Vaginal Microbiomes Alter HIV-1 Infection and Antiretroviral Efficacy in Colonized Epithelial Multilayer Cultures , 2014, PloS one.

[44]  J. Ravel,et al.  Microbiome, sex hormones, and immune responses in the reproductive tract: challenges for vaccine development against sexually transmitted infections. , 2014, Vaccine.

[45]  J. Wijgert,et al.  Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women , 2014, The ISME Journal.

[46]  N. Schmidt,et al.  Co-occurrence of Trichomonas vaginalis and Bacterial Vaginosis and Vaginal Shedding of HIV-1 RNA , 2014, Sexually transmitted diseases.

[47]  Roberto Romero,et al.  The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women , 2014, Microbiome.

[48]  B. Richardson,et al.  Bacterial Vaginosis and the Risk of Trichomonas vaginalis Acquisition Among HIV-1–Negative Women , 2014, Sexually transmitted diseases.

[49]  Ronald W. Davis,et al.  Diversity of the Vaginal Microbiome Correlates With Preterm Birth , 2014, Reproductive Sciences.

[50]  Jacques Ravel,et al.  Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis , 2013, Microbiome.

[51]  C. Kenyon,et al.  The global epidemiology of bacterial vaginosis: a systematic review. , 2013, American journal of obstetrics and gynecology.

[52]  S. Hillier,et al.  The complexity of contraceptives: understanding their impact on genital immune cells and vaginal microbiota , 2013, AIDS.

[53]  C. Fairley,et al.  The Burden of Bacterial Vaginosis: Women’s Experience of the Physical, Emotional, Sexual and Social Impact of Living with Recurrent Bacterial Vaginosis , 2013, PloS one.

[54]  J. Hocking,et al.  Hormonal Contraception Is Associated with a Reduced Risk of Bacterial Vaginosis: A Systematic Review and Meta-Analysis , 2013, PloS one.

[55]  S. Lebeer,et al.  Vaginal microbiota and its role in HIV transmission and infection. , 2013, FEMS microbiology reviews.

[56]  M. Nibert,et al.  The Villain Team-Up or how Trichomonas vaginalis and bacterial vaginosis alter innate immunity in concert , 2013, Sexually Transmitted Infections.

[57]  L. Mosca,et al.  Bacterial vaginosis: a review on clinical trials with probiotics. , 2013, The new microbiologica.

[58]  Yun-Mi Song,et al.  Association of the Vaginal Microbiota with Human Papillomavirus Infection in a Korean Twin Cohort , 2013, PloS one.

[59]  J. Ravel,et al.  Male Circumcision Significantly Reduces Prevalence and Load of Genital Anaerobic Bacteria , 2013, mBio.

[60]  Se Jin Song,et al.  Cohabiting family members share microbiota with one another and with their dogs , 2013, eLife.

[61]  S. Garland,et al.  Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[62]  R. Fichorova,et al.  Effects of feminine hygiene products on the vaginal mucosal biome , 2013, Microbial ecology in health and disease.

[63]  R. Angeletti,et al.  Lactobacillus Proteins Are Associated with the Bactericidal Activity against E. coli of Female Genital Tract Secretions , 2012, PloS one.

[64]  Jacques Ravel,et al.  Understanding vaginal microbiome complexity from an ecological perspective. , 2012, Translational research : the journal of laboratory and clinical medicine.

[65]  Zaid Abdo,et al.  Association Between Trichomonas vaginalis and Vaginal Bacterial Community Composition Among Reproductive-Age Women , 2012, Sexually transmitted diseases.

[66]  Jacques Ravel,et al.  Vaginal microbiome: rethinking health and disease. , 2012, Annual review of microbiology.

[67]  Jeanne M. Marrazzo,et al.  Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria , 2012, PloS one.

[68]  J. Menten,et al.  Quantification of bacterial species of the vaginal microbiome in different groups of women, using nucleic acid amplification tests , 2012, BMC Microbiology.

[69]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[70]  J. Marrazzo,et al.  Extravaginal reservoirs of vaginal bacteria as risk factors for incident bacterial vaginosis. , 2012, The Journal of infectious diseases.

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

[72]  P. Mirmonsef,et al.  The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract. , 2012, Current HIV research.

[73]  S. Garland,et al.  Bacterial Vaginosis (BV) Candidate Bacteria: Associations with BV and Behavioural Practices in Sexually-Experienced and Inexperienced Women , 2012, PloS one.

[74]  Jeff Kline,et al.  Architectural design influences the diversity and structure of the built environment microbiome , 2012, The ISME Journal.

[75]  R. Brotman,et al.  Vaginal microbiome and sexually transmitted infections: an epidemiologic perspective. , 2011, The Journal of clinical investigation.

[76]  M. Klebanoff,et al.  Bacterial vaginosis is associated with variation in dietary indices. , 2011, The Journal of nutrition.

[77]  K. Shah,et al.  Bacterial Vaginosis and the Natural History of Human Papillomavirus , 2011, Infectious diseases in obstetrics and gynecology.

[78]  C. Morrison,et al.  Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis , 2011, PLoS medicine.

[79]  R. Brotman,et al.  Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. , 2010, The Journal of infectious diseases.

[80]  Martina Morris,et al.  Timing Is Everything: International Variations in Historical Sexual Partnership Concurrency and HIV Prevalence , 2010, PloS one.

[81]  G. Weinstock,et al.  Characteristic Male Urine Microbiomes Associate with Asymptomatic Sexually Transmitted Infection , 2010, PloS one.

[82]  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.

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

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

[85]  T. Spagnuolo,et al.  Vaginal microbial flora and outcome of pregnancy , 2010, Archives of Gynecology and Obstetrics.

[86]  M. Krohn,et al.  Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. , 2009, Journal of NutriLife.

[87]  J. Hocking,et al.  Sexual risk factors and bacterial vaginosis: a systematic review and meta-analysis. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[88]  J. Peipert,et al.  Viral Sexually Transmitted Infections and Bacterial Vaginosis: 2001–2004 National Health and Nutrition Examination Survey Data , 2008, Sexually transmitted diseases.

[89]  A. Adimora,et al.  Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies , 2008, AIDS.

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

[91]  J. Peipert,et al.  Bacterial Vaginosis, Race, and Sexually Transmitted Infections: Does Race Modify the Association? , 2008, Sexually transmitted diseases.

[92]  L. Meyn,et al.  A Delicate Balance: Risk Factors for Acquisition of Bacterial Vaginosis Include Sexual Activity, Absence of Hydrogen Peroxide-Producing Lactobacilli, Black Race, and Positive Herpes Simplex Virus Type 2 Serology , 2008, Sexually transmitted diseases.

[93]  M. Klebanoff,et al.  Longitudinal Association Between Hormonal Contraceptives and Bacterial Vaginosis in Women of Reproductive Age , 2007, Sexually transmitted diseases.

[94]  G. Mcquillan,et al.  The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001-2004. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[95]  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.

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

[97]  M. Klebanoff,et al.  Dietary intake of selected nutrients affects bacterial vaginosis in women. , 2007, The Journal of nutrition.

[98]  S. Aral,et al.  Drivers of STD/HIV epidemiology and the timing and targets of STD/HIV prevention , 2007, Sexually Transmitted Infections.

[99]  R. Desmond,et al.  A randomized trial of metronidazole in asymptomatic bacterial vaginosis to prevent the acquisition of sexually transmitted diseases. , 2007, American journal of obstetrics and gynecology.

[100]  A. Ouedraogo,et al.  Association between bacterial vaginosis and Herpes simplex virus type-2 infection: implications for HIV acquisition studies , 2007, Sexually Transmitted Infections.

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

[102]  D. Eschenbach.  Bacterial vaginosis: resistance, recurrence, and/or reinfection? , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[103]  Irene A. Doherty,et al.  Concurrent sexual partnerships among men in the United States. , 2007, American journal of public health.

[104]  K. Peeyananjarassri,et al.  Selection and identification of anaerobic lactobacilli producing inhibitory compounds against vaginal pathogens. , 2006, FEMS immunology and medical microbiology.

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

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

[107]  J. Schwebke.  Abnormal vaginal flora as a biological risk factor for acquisition of HIV infection and sexually transmitted diseases. , 2005, The Journal of infectious diseases.

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

[109]  G. Claeys,et al.  Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy , 2005, BMC infectious diseases.

[110]  J. Palefsky,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. , 2005, The Journal of infectious diseases.

[111]  E. Bukusi,et al.  Detection of novel organisms associated with salpingitis, by use of 16S rDNA polymerase chain reaction. , 2004, The Journal of infectious diseases.

[112]  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.

[113]  R. Ness,et al.  Bacterial Vaginosis and Risk of Pelvic Inflammatory Disease , 2004, Obstetrics and gynecology.

[114]  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.

[115]  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.

[116]  D R Holtgrave,et al.  Social capital, poverty, and income inequality as predictors of gonorrhoea, syphilis, chlamydia and AIDS case rates in the United States , 2003, Sexually transmitted infections.

[117]  A. Jerse,et al.  Inhibition of Neisseria gonorrhoeae by Lactobacillus Species That Are Commonly Isolated from the Female Genital Tract , 2002, Infection and Immunity.

[118]  P. Braveman,et al.  The relationship of neighborhood socioeconomic characteristics to birthweight among 5 ethnic groups in California. , 2001, American journal of public health.

[119]  R. Sweet,et al.  Risk factors associated with pelvic inflammatory disease of differing microbial etiologies , 1994, Obstetrics and gynecology.

[120]  D. Johnson,et al.  Observations concerning the microbial etiology of acute salpingitis. , 1994, American journal of obstetrics and gynecology.

[121]  C. Kenyon,et al.  Strong association between the prevalence of bacterial vaginosis and male point-concurrency. , 2014, European journal of obstetrics, gynecology, and reproductive biology.

[122]  N. Sewankambo,et al.  The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. , 2009, American journal of obstetrics and gynecology.