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The Main Disruptors of the Vaginal Microbiome: A Research Analysis

The scientific literature is missing an extensive review of vaginal microbiome disruptors. So, we took it upon ourselves to close this knowledge gap and create one.

9 minutes

60 Citations

The vaginal microbiome (VMB) is the foundation of gynecological, urogenital, and reproductive health. A growing body of research demonstrates that the vaginal microbiome is easily disturbed by day-to-day activities, but an extensive review of VMB disruptors is missing in scientific literature. So, we took it upon ourselves to close this knowledge gap and create one. 

To do so, our R&D team analyzed the highest-resolution dataset9 ever collected on the vaginal microbiome by Dr. Jacques Ravel, a leading VMB researcher. Then, we conducted a highly comprehensive literature survey of existing scientific research. The result is the following reference paper—a detailed summary of primary and secondary disruptors to the vaginal microbiome.

Introduction

The vaginal microbiome (VMB) is the foundation of gynecological, urogenital, and reproductive health. However, this ecosystem of microbes is easily disrupted and can shift regularly, leaving the vagina susceptible to imbalances and discomforts. Optimal VMBs are typically characterized by low microbial diversity and a high abundance of Lactobacillus species.1 Lactobacillus-dominated VMBs are categorized into “community state types” (CSTs) defined by their taxonomic composition: Lactobacillus crispatus-dominated (CST I), L. gasseri-dominated (CST II), L. iners-dominated (CST III), and L. jensenii-dominated (CST V).2 CST IV VMBs are defined by low levels of lactobacilli and the dominance of diverse anaerobes.

Optimal L. crispatus-dominated CST I VMBs are associated with decreased risk of bacterial vaginosis (BV), vulvovaginal candidiasis, sexually transmitted infections (STIs), as well as favorable fertility outcomes and reduced risk of adverse pregnancy events such as preterm birth.3,4 CST IV VMBs are epidemiologically associated with an increased risk of adverse genitourinary and obstetric outcomes, including spontaneous preterm birth, low birth weight and sexually transmitted infections (STIs), pelvic inflammatory disease, urinary tract infections, cervical intraepithelial neoplasia, and infertility.1,4-8

Given the extensive evidence substantiating the connection between CST I and vaginal health, it is of substantial interest to assess the impact of daily factors and common disruptions on the composition and stability of the vaginal microbiome. Two complementary approaches were taken to address this issue. First, we analyzed the most comprehensive, highest-resolution dataset yet collected on the vaginal microbiome, which is uniquely well-suited to address the day-to-day impact of disruptors on the vaginal microbiome.9 In this cohort, 130 individuals collected vaginal samples over a 70-day period while also completing a detailed questionnaire on their day-to-day habits. Second, a comprehensive literature search was conducted to ascertain expert consensus on the impact of vaginal perturbations on the vaginal microbiome.

Key Findings

Analysis of the VMB cohort indicates that 90% of women have an unstable vaginal microbiome when stability is defined as being in an optimal microbiome state (CST I, dominated by Lactobacillus crispatus) for 90% of the time or more.9,10 This definition of vaginal microbiome stability is also reinforced by the finding that CST I microbiomes are the most stable and demonstrate the lowest probability (2%) of shifting to a dysbiotic, non-optimal CST-IV configuration of all Lactobacillus-dominated CSTs (compared with 5.6% for L. gasseri-dominated CST II and L. iners-dominated CST III). This aligns with the broader finding in the field that L. crispatus-dominated microbiomes tend to be more resistant to disruptions compared to other vaginal microbiome type .10

Impacts of Disturbances on Vaginal Microbiome Stability

Based on the analysis of the VMB cohort and a deep review of the literature, several key disruptors common in daily life were identified as being associated with vaginal microbiome instability. The primary factors most strongly associated with microbiome instability included vaginal intercourse, menstruation, condom use, sex toy use, oral sex, lubricant use, use of certain prescriptions, contraceptives, cleansers, and feminine hygiene products. In addition to these daily disruptors, the literature demonstrates that the postpartum period is associated with potential shifts away from an optimal CST I microbiome. Additional factors associated with vaginal microbiome changes in literature include exercise, stress, and diet. 

Disruptors of the Vaginal Microbiome 

Primary Disruptors of the Vaginal Microbiome: 

Sex

Menstruation

Condom use

Sex Toys

Oral Sex

Gels and Lubricants

Certain Contraceptives

Certain Prescriptions

Certain Cleansers

Feminine Hygiene Products

Past Pregnancy/ Postpartum

Primary disruptors have been linked/associated with imbalances in the vaginal microbiome and can include activities that are part of day-to-day life and/or cyclical hormonal variations. Primary disruptors include natural hormonal cycles, medications that alter hormonal cycles, and activities that involve the introduction of inter-/intravaginal products to the vagina. 

Sexual activity has been shown to directly impact the vaginal microbiome, increasing the prevalence of non-optimal vaginal species, such as L. iners and Gardnerella vaginalis, and reducing the concentration of L. crispatus.11,12 Sexual partners can also be a source for the re-introduction of non-optimal bacterial species. For example, vaginal dysbiosis-associated bacteria are detected in men who have vaginal sex.13 Notably, the penile microbiota is predictive for BV incidence in female sex partners, and the incidence of BV among women who have sex with women is high.14,15 Vaginal intercourse was strongly associated with changes from CST I to non-optimal CSTs in the VMB cohort (p < 0.001)). 

Sexual behaviors can also shape the vaginal microbiome. Use of condoms is inversely associated with L. iners-dominated CST-III, and associated with L. crispatus colonization.16,17 Frequent use of sex toys (defined as >10 toy-vaginal acts in the past 3 months) can also cause disruption by increasing the colonization of vaginal pathogens such as G. vaginalis, and reducing the abundance of Lactobacillus spp.18 Oral sex with a female partner is associated with an increased risk of BV in a dose-dependent response with increasing number of episodes.19 Use of lubricant products containing chlorhexidine gluconate or nonoxynol-9 inhibit Lactobacillus spp. growth, while lubricants that do not directly impact bacterial growth can still substantially decrease attachment of beneficial L. crispatus to the vaginal epithelium.20 Mean relative abundance of L. crispatus decreased for those who used lubricants, especially those that were CST-III L. iners-dominated prior to exposure.21 These findings were substantiated in the VMB cohort, where condom use, oral sex, sex toy use, and lubricant use were all significantly associated with changes in CST (p < 0.05).

Hormonal cycles can also drive vaginal microbiome change, where even individuals with optimal CSTs can transition to less protective states during menses and Lactobacillus spp. decrease in abundance.10,22 Menstruation was strongly associated with changes in CST state over short timescales in the VMB cohort (p<0.001). Postpartum hormonal changes drive shifts in the vaginal microbiome with an increase in mixed species and a decrease in Lactobacillus spp. observed postpartum versus in the third trimester.23 A survey of American women showed that 77% of postpartum vaginal communities contain a mix of non-optimal species, including G. vaginalis and Prevotella, and low proportions of Lactobacillus spp.24 Overall, studies show that postpartum vaginal microbiome samples have reduced levels of lactobacilli, a complex mixed species community, and increased microbial diversity.25,26 

Vaginal products, including certain contraceptives, prescriptions, and cleansers can disrupt the vaginal microbiome. A stable vaginal microbiome is promoted by oral contraceptives, contraceptive injections (Depot Medroxyprogesterone),  hormonal-IUDs (Levonorgestrel), and NuvaRing implant while a higher prevalence of BV is observed in women using non-hormonal copper IUDs.27-36 A decrease in the prevalence of lactobacilli is observed with spermicide use.37,38 Prescriptions, such as antibiotics, can completely reorganize the vaginal microbiome, even after one day of initiating therapy, and is the standard-of-care to treat BV infections (CDC).39 Cleansers may do more harm than good, as vaginal washing has been associated with an increased risk of BV and HIV acquisition.40-45

Menstrual products and feminine hygiene practices can also result in vaginal microbiome disruption. Menstrual cups have been positively associated with the presence of  L. crispatus, while menstrual pads were negatively associated with L. crispatus (and positively associated with Prevotella, especially when used in the past 48 hrs.). In addition, pubic shaving is associated with lower levels of non-optimal species.46 While the effect of douching on the vaginal microbiome depended on the product used, in general, douching increases the amount of non-optimal bacteria and increases the risk of BV.44,47-50

Secondary Disruptors of the Vaginal Microbiome: 

Diet

Stress

Exercise 

Swimming

Secondary disruptors have also been linked to disruptions of the vaginal microbiome, and include more systemic influences, such as exercise, diet, and stress.

Exercise has been observed to trend with diversity of the vaginal microbiome; for low to moderate intensity, the average Shannon Index (a measure of species diversity) increased with exercise time.51 While many non-scientific resources online link swimming with disruption of the vaginal microbiome, there is limited data substantiating the link. Relevant data includes the detection of Candida spp. in swimming pool facilities, a possible connection between tight-fitting/poorly ventilated undergarments and vulvovaginal candidiasis (VVC), and studies demonstrating that the skin microbiome is impacted by swimming.52-57 

In terms of diet, higher consumption of low-fat dairy is associated with increased likelihood of an optimal vaginal microbiome state.58 In a recent citizen-science project (ISALA), sugary beverages and meat were linked with lower levels of L. crispatus, and a high frequency of vegetable consumption in the past 24 hrs. was associated with higher levels of L. crispatus.46

Stress has also been linked to vaginal microbiome changes, with increased perceived stress associated with greater odds of BV incidence.59 In a separate study, a 5-unit increase in the Cohen’s Perceived Stress Scale was associated with greater risks of transitioning from the L. iners-dominated community state type (26% higher) to BV or maintaining BV from baseline. The inverse was also true—women with baseline BV reporting a 5-unit stress increase were less likely to transition to microbiota dominated by L. crispatus, L. gasseri, or L. jensenii.60

Methods: VMB Cohort Analysis

We analyzed high-resolution vaginal microbiome data collected for 130 individuals over a 70-day period, to determine overall microbiome stability and the impacts of lifestyle disturbances tracked in a cohort questionnaire. 

Vaginal microbiome stability was assessed using the proportion of non-menstrual timepoints each subject spent in community state type I (CST I). The stability score was defined as the number of non-menstrual timepoints in CST I divided by the total number of non-menstrual timepoints for each subject. We found that subjects who spent less than 90% of their time in CST I (L. crispatus dominated microbiomes) represented 90% of the total population in the cohort. As a secondary measure of microbiome stability, we also assessed the overall probability of transitioning between CSTs. We found that CST I, which is roughly defined by a dominance of L. crispatus, is the most stable, with the lowest probability of shifting to any other state (2%). 

This dataset includes detailed questionnaire data tracking the occurrence of common disruptors that can be used to directly investigate the relationship between disruptors, and the number of CST changes observed (a measure of microbiome instability). To do so, a sliding window approach was used. For each subject, whenever a transition between CSTs occurred, the number of reports of each tracked event (e.g., sexual behaviors, feminine hygiene practices, menstruation, etc.) within a window of 7 timepoints preceding the transition was summed. The total event count within all windows within a participant was then directly correlated with the number of transitions per subject, allowing for a ranking of the association between various factors and instability. 

Citations

  1. Hillier, S. L., Krohn, M. A., Rabe, L. K., Klebanoff, S. J., & Eschenbach, D. A. (1993). The normal vaginal flora, H2O2-producing Lactobacilli, and bacterial vaginosis in pregnant women. Clinical Infectious Diseases, 16(Supplement_4), S273–S281. https://doi.org/10.1093/clinids/16.supplement_4.s273
  2. Ravel, J., Gajer, P., Abdo, Z., Schneider, G. M., Koenig, S. S. K., McCulle, S. L., Karlebach, S., Gorle, R., Russell, J., Tacket, C. O., Brotman, R. M., Davis, C. C., Ault, K., Peralta, L., & Forney, L. J. (2010). Vaginal microbiome of reproductive-age women. Proceedings of the National Academy of Sciences of the United States of America, 108(supplement_1), 4680–4687. https://doi.org/10.1073/pnas.1002611107
  3. Petrova, M. I., Van Den Broek, M., Balzarini, J., Vanderleyden, J., & Lebeer, S. (2013). Vaginal microbiota and its role in HIV transmission and infection. FEMS Microbiology Reviews, 37(5), 762–792. https://doi.org/10.1111/1574-6976.12029
  4. Fettweis, J. M., Serrano, M. G., Brooks, J. P., Edwards, D. J., Girerd, P. H., Parikh, H. I., Huang, B., Arodz, T. J., Edupuganti, L., Glascock, A. L., Xu, J., Jimenez, N. R., Vivadelli, S. C., Fong, S. S., Sheth, N. U., Jean, S., Lee, V., Bokhari, Y. A., Lara, A. M., . . . Buck, G. A. (2019). The vaginal microbiome and preterm birth. Nature Medicine, 25(6), 1012–1021. https://doi.org/10.1038/s41591-019-0450-2
  5. Wiesenfeld, H. C., Hillier, S. L., Krohn, M. A., Amortegui, A. J., Heine, R. P., Landers, D. V., & Sweet, R. L. (2002). Lower genital tract infection and endometritis. Obstetrics and Gynecology, 100(3), 456–463. https://doi.org/10.1097/00006250-200209000-00011
  6. Sobel, J. D., Kaur, N., Woznicki, N. A., Boikov, D., Aguin, T., Gill, G., & Akins, R. A. (2019). Prognostic indicators of recurrence of bacterial vaginosis. Journal of Clinical Microbiology, 57(5). https://doi.org/10.1128/jcm.00227-19
  7. Mitra, A., MacIntyre, D. A., Paraskevaidi, M., Moscicki, A., Mahajan, V., Smith, A., Lee, Y. S., Lyons, D., Paraskevaidis, E., Marchesi, J. R., Bennett, P. R., & Kyrgiou, M. (2021). The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia. Genome Medicine, 13(1). https://doi.org/10.1186/s13073-021-00977-w
  8. Mania-Pramanik, J., Kerkar, S. C., & Salvi, V. S. (2009). Bacterial vaginosis: A cause of infertility? International Journal of STD & AIDS, 20(11), 778–781. https://doi.org/10.1258/ijsa.2009.009193
  9. Ravel, J., Brotman, R. M., Gajer, P., Ma, B., Nandy, M., Fadrosh, D. W., Sakamoto, J., Koenig, S. S., Fu, L., Zhou, X., Hickey, R. J., Schwebke, J. R., & Forney, L. J. (2013). Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome, 1(1). https://doi.org/10.1186/2049-2618-1-29
  10. Gajer, P., Brotman, R. M., Bai, G., Sakamoto, J., Schütte, U. M., Zhong, X., Koenig, S. S., Fu, L., Ma, Z. S., Zhou, X., Abdo, Z., Forney, L. J., & Ravel, J. (2012). Temporal dynamics of the human vaginal microbiota. Science Translational Medicine, 4(132), 132ra52. https://doi.org/10.1126/scitranslmed.3003605
  11. Vodstrcil, L. A., Twin, J., Garland, S. M., Fairley, C. K., Hocking, J. S., Law, M. G., Plummer, E. L., Fethers, K. A., Chow, E. P. F., Tabrizi, S. N., & Bradshaw, C. S. (2017). The influence of sexual activity on the vaginal microbiota and Gardnerella vaginalis clade diversity in young women. PLoS One, 12(2), e0171856. https://doi.org/10.1371/journal.pone.0171856
  12. Jespers, V., van de Wijgert, J., Cools, P., Verhelst, R., Verstraelen, H., Delany-Moretlwe, S., Mwaura, M., Ndayisaba, G. F., Mandaliya, K., Menten, J., Hardy, L., Crucitti, T., & Vaginal Biomarkers Study Group (2015). 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. BMC Infectious Diseases, 15, 115. https://doi.org/10.1186/s12879-015-0825-z
  13. Toh, E., Xing, Y., Gao, X., Jordan, S. J., Batteiger, T. A., Batteiger, B. E., Van Der Pol, B., Muzny, C. A., Gebregziabher, N., Williams, J. A., Fortenberry, L. J., Fortenberry, J. D., Dong, Q., & Nelson, D. E. (2023). Sexual behavior shapes male genitourinary microbiome composition. Cell Reports Medicine, 4(3), 100981. https://doi.org/10.1016/j.xcrm.2023.100981
  14. Mehta, S. D., Zhao, D., Green, S. J., Agingu, W., Otieno, F., Bhaumik, R., Bhaumik, D., & Bailey, R. C. (2020). The microbiome composition of a man’s penis predicts incident bacterial vaginosis in his female sex partner with high accuracy. Frontiers in Cellular and Infection Microbiology, 10. https://doi.org/10.3389/fcimb.2020.00433
  15. Plummer, E. L., Vodstrcil, L. A., Fairley, C. K., Tabrizi, S. N., Garland, S. M., Law, M. G., Hocking, J. S., Fethers, K. A., Bulach, D. M., Murray, G. L., & Bradshaw, C. S. (2019). Sexual practices have a significant impact on the vaginal microbiota of women who have sex with women. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-55929-7
  16. Novak, J., Ravel, J., Ma, B., Ferreira, C. S. T., Tristão, A. D. R., Silva, M. G., & Marconi, C. (2022). Characteristics associated with Lactobacillus iners-dominated vaginal microbiota. Sexually Transmitted Infections, 98(5), 353–359. https://doi.org/10.1136/sextrans-2020-054824
  17. Ma, B., Forney, L. J., & Ravel, J. (2012). Vaginal microbiome: Rethinking health and disease. Annual Review of Microbiology, 66(1), 371–389. https://doi.org/10.1146/annurev-micro-092611-150157
  18. Mitchell, C., Manhart, L. E., Thomas, K. K., Agnew, K., & Marrazzo, J. M. (2011). Effect of sexual activity on vaginal colonization with hydrogen peroxide-producing Lactobacilli and Gardnerella vaginalis. Sexually Transmitted Diseases, 38(12), 1137–1144. https://doi.org/10.1097/olq.0b013e31822e6121
  19. Marrazzo, J. M., Thomas, K. K., Fiedler, T. L., Ringwood, K., & Fredricks, D. N. (2010). Risks for acquisition of bacterial vaginosis among women who report sex with women: A cohort study. PLoS One, 5(6), e11139. https://doi.org/10.1371/journal.pone.0011139
  20. Laniewski, P., Owen, K. A., Khnanisho, M., Brotman, R. M., & Herbst-Kralovetz, M. M. (2020). Clinical and personal lubricants impact the growth of vaginal Lactobacillus species and colonization of vaginal epithelial cells: An in vitro study. Sexually Transmitted Diseases, 48(1), 63–70. https://doi.org/10.1097/olq.0000000000001272
  21. Tuddenham, S., Stennett, C. A., Cone, R. A., Ravel, J., Macintyre, A. N., Ghanem, K. G., He, X., & Brotman, R. M. (2021). Vaginal cytokine profile and microbiota before and after lubricant use compared with condomless vaginal sex: A preliminary observational study. BMC Infectious Diseases, 21(1). https://doi.org/10.1186/s12879-021-06512-x
  22. Santiago, G. L. D. S., Tency, I., Verstraelen, H., Verhelst, R., Trog, M., Temmerman, M., Vancoillie, L., Decat, E., Cools, P., & Vaneechoutte, M. (2012). Longitudinal qPCR study of the dynamics of L. crispatus, L. iners, A. vaginae, (sialidase positive) G. vaginalis, and P. bivia in the vagina. PLoS One, 7(9), e45281. https://doi.org/10.1371/journal.pone.0045281
  23. Pace, R. M., Chu, D. M., Prince, A. L., Ma, J., Seferovic, M. D., & Aagaard, K. M. (2021). Complex species and strain ecology of the vaginal microbiome from pregnancy to postpartum and association with preterm birth. Med, 2(9), 1027-1049.e7. https://doi.org/10.1016/j.medj.2021.06.001
  24. Nunn, K. L., Witkin, S. S., Schneider, G. M., Boester, A., Nasioudis, D., Minis, E., Gliniewicz, K., & Forney, L. J. (2021). Changes in the vaginal microbiome during the pregnancy to postpartum transition. Reproductive Sciences, 28(7), 1996–2005. https://doi.org/10.1007/s43032-020-00438-6
  25. Doyle, R., Gondwe, A., Fan, Y., Maleta, K., Ashorn, P., Klein, N., & Harris, K. (2018). A Lactobacillus-deficient vaginal microbiota dominates postpartum women in rural Malawi. Applied and Environmental Microbiology, 84(6). https://doi.org/10.1128/aem.02150-17
  26. Zhang, Y., Yang, H., Lin, L., Yang, W., Xiong, G., & Gao, G. (2022). The relationship between pelvic floor functions and vaginal microbiota in 6–8 weeks postpartum women. Frontiers in Microbiology, 13. https://doi.org/10.3389/fmicb.2022.975406
  27. Aagaard, K., Riehle, K., Ma, J., Segata, N., Mistretta, T. A., Coarfa, C., Raza, S., Rosenbaum, S., Van Den Veyver, I., Milosavljevic, A., Gevers, D., Huttenhower, C., Petrosino, J., & Versalovic, J. (2012). A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One, 7(6), e36466. https://doi.org/10.1371/journal.pone.0036466
  28. van de Wijgert, J. H., Verwijs, M. C., Turner, A. N., & Morrison, C. S. (2013). Hormonal contraception decreases bacterial vaginosis but oral contraception may increase candidiasis: Implications for HIV transmission. AIDS, 27(13), 2141–2153. https://doi.org/10.1097/QAD.0b013e32836290b6
  29. Brooks, J. P., Edwards, D. J., Blithe, D. L., Fettweis, J. M., Serrano, M. G., Sheth, N. U., Strauss, J. F., Buck, G. A., & Jefferson, K. K. (2017). Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome. Contraception, 95(4), 405–413. https://doi.org/10.1016/j.contraception.2016.11.006
  30. Jacobson, J. C., Turok, D. K., Dermish, A. I., Nygaard, I. E., & Settles, M. L. (2014). Vaginal microbiome changes with levonorgestrel intrauterine system placement. Contraception, 90(2), 130–135. https://doi.org/10.1016/j.contraception.2014.04.006
  31. Hashway, S. A., Bergin, I. L., Bassis, C. M., Uchihashi, M., Schmidt, K. C., Young, V. B., Aronoff, D. M., Patton, D. L., & Bell, J. D. (2013). Impact of a hormone‐releasing intrauterine system on the vaginal microbiome: A prospective baboon model. Journal of Medical Primatology, 43(2), 89–99. https://doi.org/10.1111/jmp.12090
  32. Bassis, C. M., Allsworth, J. E., Wahl, H. N., Sack, D. E., Young, V. B., & Bell, J. D. (2017). Effects of intrauterine contraception on the vaginal microbiota. Contraception, 96(3), 189–195. https://doi.org/10.1016/j.contraception.2017.05.017
  33. Achilles, S. L., Austin, M. N., Meyn, L. A., Mhlanga, F., Chirenje, Z. M., & Hillier, S. L. (2018). Impact of contraceptive initiation on vaginal microbiota. American Journal of Obstetrics and Gynecology, 218(6), 622.e1-622.e10. https://doi.org/10.1016/j.ajog.2018.02.017
  34. Pelzer, E. S., Willner, D., Buttini, M., & Huygens, F. (2018). A role for the endometrial microbiome in dysfunctional menstrual bleeding. Antonie Van Leeuwenhoek, 111(6), 933–943. https://doi.org/10.1007/s10482-017-0992-6
  35. Srinivasan, S., Liu, C., Mitchell, C. M., Fiedler, T. L., Thomas, K. K., Agnew, K. J., Marrazzo, J. M., & Fredricks, D. N. (2010). Temporal variability of human vaginal bacteria and relationship with bacterial vaginosis. PLoS One, 5(4), e10197. https://doi.org/10.1371/journal.pone.0010197
  36. Peebles, K., Kiweewa, F. M., Palanee-Phillips, T., Chappell, C., Singh, D., Bunge, K. E., Naidoo, L., Makanani, B., Jeenarain, N., Reynolds, D., Hillier, S. L., Brown, E. R., Baeten, J. M., Balkus, J. E., Baeten, J., Palanee-Phillips, T., Brown, E., Soto-Torres, L., Schwartz, K., . . . Mhlanga, F. (2021). Elevated risk of bacterial vaginosis among users of the copper intrauterine device: A prospective longitudinal cohort study. Clinical Infectious Diseases, 73(3), 513–520. https://doi.org/10.1093/cid/ciaa703
  37. Wilkinson, D., Tholandi, M., Ramjee, G., & Rutherford, G. W. (2002). Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: Systematic review and meta-analysis of randomised controlled trials including more than 5000 women. The Lancet Infectious Diseases, 2(10), 613–617. https://doi.org/10.1016/s1473-3099(02)00396-1
  38. Schreiber, C. A., Meyn, L. A., Creinin, M. D., Barnhart, K. T., & Hillier, S. L. (2006). Effects of long-term use of nonoxynol-9 on vaginal flora. Obstetrics and Gynecology, 107(1), 136–143. https://doi.org/10.1097/01.aog.0000189094.21099.4a
  39. Mayer, B. T., Srinivasan, S., Fiedler, T. L., Marrazzo, J. M., Fredricks, D. N., & Schiffer, J. T. (2015). Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial vaginosis. The Journal of Infectious Diseases, 212(5), 793–802. https://doi.org/10.1093/infdis/jiv079
  40. Hassan, W. M., Lavreys, L., Chohan, V., Richardson, B. A., Mandaliya, K., Ndinya-Achola, J. O., Kiarie, J., Jaoko, W., Holmes, K. K., & McClelland, R. S. (2007). Associations between intravaginal practices and bacterial vaginosis in Kenyan female sex workers without symptoms of vaginal infections. Sexually Transmitted Diseases, 34(6), 384–388. https://doi.org/10.1097/01.olq.0000243624.74573.63
  41. Low, N., Chersich, M. F., Schmidlin, K., Egger, M., Francis, S. C., Van De Wijgert, J. H. H. M., Hayes, R. J., Baeten, J. M., Brown, J., Delany-Moretlwe, S., Kaul, R., McGrath, N., Morrison, C., Myer, L., Temmerman, M., Van Der Straten, A., Watson-Jones, D., Zwahlen, M., & Hilber, A. M. (2011). Intravaginal practices, bacterial vaginosis, and HIV infection in women: Individual participant data meta-analysis. PLoS Medicine, 8(2), e1000416. https://doi.org/10.1371/journal.pmed.1000416
  42. McClelland, R. S., Richardson, B. A., Hassan, W. M., Chohan, V., Lavreys, L., Mandaliya, K., Kiarie, J., Jaoko, W., Ndinya‐Achola, J. O., Baeten, J. M., Kurth, A. E., & Holmes, K. K. (2008). Improvement of vaginal health for Kenyan women at risk for acquisition of human immunodeficiency virus type 1: Results of a randomized trial. The Journal of Infectious Diseases, 197(10), 1361–1368. https://doi.org/10.1086/587490
  43. Baeten, J. M., Hassan, W. M., Chohan, V., Richardson, B. A., Mandaliya, K., Ndinya-Achola, J. O., Jaoko, W., & McClelland, R. S. (2009). Prospective study of correlates of vaginal Lactobacillus colonisation among high-risk HIV-1 seronegative women. Sexually Transmitted Infections, 85(5), 348–353. https://doi.org/10.1136/sti.2008.035451
  44. Brotman, R. M., Klebanoff, M. A., Nansel, T. R., Andrews, W. W., Schwebke, J. R., Zhang, J., Yu, K. F., Zenilman, J. M., & Scharfstein, D. O. (2008). A longitudinal study of vaginal douching and bacterial vaginosis–A marginal structural modeling analysis. American Journal of Epidemiology, 168(2), 188–196. https://doi.org/10.1093/aje/kwn103
  45. McClelland, R. S., Lavreys, L., Hassan, W. M., Mandaliya, K., Ndinya-Achola, J. O., & Baeten, J. M. (2006). Vaginal washing and increased risk of HIV-1 acquisition among African women: A 10-year prospective study. AIDS, 20(2), 269–273. https://doi.org/10.1097/01.aids.0000196165.48518.7b
  46. Lebeer, S., Ahannach, S., Gehrmann, T., Wittouck, S., Eilers, T., Oerlemans, E., Condori, S., Dillen, J., Spacova, I., Donck, L. V., Masquillier, C., Allonsius, C. N., Bron, P. A., Van Beeck, W., De Backer, C., Donders, G., & Verhoeven, V. (2023). A citizen-science-enabled catalogue of the vaginal microbiome and associated factors. Nature Microbiology, 8(11), 2183–2195. https://doi.org/10.1038/s41564-023-01500-0
  47. Ness, R. (2002). Douching in relation to bacterial vaginosis, Lactobacilli, and facultative bacteria in the vagina. Obstetrics and Gynecology, 100(4), 765–772. https://doi.org/10.1016/s0029-7844(02)02184-1
  48. Van Der Veer, C., Bruisten, S. M., Van Houdt, R., Matser, A. A., Tachedjian, G., Van De Wijgert, J. H. H. M., De Vries, H. J. C., & Van Der Helm, J. J. (2019). Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota. BMC Microbiology, 19(1). https://doi.org/10.1186/s12866-019-1545-0
  49. Hesham, H., Mitchell, A. J., Bergerat, A., Hung, K., & Mitchell, C. M. (2021). Impact of vaginal douching products on vaginal Lactobacillus, Escherichia coli and epithelial immune responses. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-02426-5
  50. Brown, S. E., He, X., Shardell, M. D., Ravel, J., Ghanem, K. G., Zenilman, J. M., & Brotman, R. M. (2023). Douching cessation and molecular bacterial vaginosis: A reanalysis of archived specimens. Sexually Transmitted Infections, 99(3), 156–161. https://doi.org/10.1136/sextrans-2022-055459
  51. Song, S. D., Acharya, K. D., Zhu, J. E., Deveney, C. M., Walther-Antonio, M. R. S., Tetel, M. J., & Chia, N. (2020). Daily vaginal microbiota fluctuations associated with natural hormonal cycle, contraceptives, diet, and exercise. MSphere, 5(4). https://doi.org/10.1128/msphere.00593-20
  52. Ekowati, Y., Ferrero, G., Kennedy, M. D., De Roda Husman, A. M., & Schets, F. M. (2018). Potential transmission pathways of clinically relevant fungi in indoor swimming pool facilities. International Journal of Hygiene and Environmental Health, 221(8), 1107–1115. https://doi.org/10.1016/j.ijheh.2018.07.013
  53. De Holanda, A. a. R., Fernandes, A. C. S., Bezerra, C. M., Ferreira, M. Â. F., De Holanda, M. R. R., De Campos Pipolo Holanda, J., & Milan, E. P. (2007). Candidíase vulvovaginal: Sintomatologia, fatores de risco e colonização anal concomitante. Revista Brasileira De Ginecologia E Obstetrícia, 29(1). https://doi.org/10.1590/s0100-72032007000100002
  54. Corsello, S., Spinillo, A., Osnengo, G., Penna, C., Guaschino, S., Beltrame, A., Blasi, N., & Festa, A. (2003). An epidemiological survey of vulvovaginal candidiasis in Italy. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 110(1), 66–72. https://doi.org/10.1016/s0301-2115(03)00096-4
  55. Patel, D. A., Gillespie, B., Sobel, J. D., Leaman, D., Nyirjesy, P., Weitz, M. V., & Foxman, B. (2004). Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: Results of a prospective cohort study. American Journal of Obstetrics and Gynecology, 190(3), 644–653. https://doi.org/10.1016/j.ajog.2003.11.027
  56. Morss‐Walton, P. C., McGee, J. S., Santillan, M. R., Kimball, R., Cukras, A., Patwardhan, S. V., Porter, M. L., & Kimball, A. B. (2022). Yin and Yang of skin microbiota in “swimmer acne.” Experimental Dermatology, 31(6), 899–905. https://doi.org/10.1111/exd.14535
  57. Nielsen, M. C., Wang, N., & Jiang, S. C. (2021). Acquisition of antibiotic resistance genes on human skin after swimming in the ocean. Environmental Research, 197, 110978. https://doi.org/10.1016/j.envres.2021.110978
  58. Rosen, E. M., Martin, C. L., Siega‐Riz, A. M., Dole, N., Basta, P. V., Serrano, M., Fettweis, J., Wu, M., Sun, S., Thorp, J. M., Buck, G., Fodor, A. A., & Engel, S. M. (2021). Is prenatal diet associated with the composition of the vaginal microbiome? Paediatric and Perinatal Epidemiology, 36(2), 243–253. https://doi.org/10.1111/ppe.12830
  59. Nansel, T. R., Riggs, M. A., Yu, K., Andrews, W. W., Schwebke, J. R., & Klebanoff, M. A. (2006). The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort. American Journal of Obstetrics and Gynecology, 194(2), 381–386. https://doi.org/10.1016/j.ajog.2005.07.047
  60. Turpin, R., Slopen, N., Borgogna, J. C., Yeoman, C. J., He, X., Miller, R. S., Klebanoff, M. A., Ravel, J., & Brotman, R. M. (2021). Perceived stress and molecular bacterial vaginosis in the National Institutes of Health longitudinal study of vaginal flora. American Journal of Epidemiology, 190(11), 2374–2383. https://doi.org/10.1093/aje/kwab147