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Bacterial vaginosis (BV) is one of the most common causes of vaginal symptoms in US women, but its causal mechanism has not yet been defined. BV is more prevalent in women who are immunosuppressed, and several risk factors for the development of BV are associated with lower quantities of immune mediators in vaginal fluid. In contrast, the poor reproductive health outcomes associated with BV, such as preterm birth and human immunodeficiency virus type 1 acquisition, are associated with increased levels of proinflammatory immune mediators in the genital tract. In this article, we discuss how variations in the host immune profile and environmental effects on host immunity may influence the risk of BV, as well as the risk of complications associated with BV.

At mucosal surfaces throughout the body mucus and mucins regulate interactions between epithelia and both commensal and pathogenic bacteria. Although the microbes in the female genital tract have been linked to multiple reproductive health outcomes, the role of cervicovaginal mucus in regulating genital tract microbes is largely unexplored. Mucus-microbe interactions could support the predominance of specific bacterial species and, conversely, commensal bacteria can influence mucus properties and its influence on reproductive health. Herein, we discuss the current evidence for both synergistic and antagonistic interactions between cervicovaginal mucus and the female genital tract microbiome, and how an improved understanding of these relationships could significantly improve women’s health.

Little is known about short-term bacterial fluctuations in the human vagina. This study used PCR to assess the variability in concentrations of key vaginal bacteria in healthy women and the immediate response to antibiotic treatment in women with bacterial vaginosis (BV). Twenty-two women assessed for BV using Amsel's criteria were evaluated daily for 7 or 14 days, then at 2, 3 and 4 weeks, using a panel of 11 bacterium-specific quantitative PCR assays. Participants with BV were treated with 5 days of intravaginal metronidazole. Participants without BV had vaginal biotas dominated by lactobacilli, whose levels fluctuated with menses. With onset of menstruation, quantities of Lactobacillus jensenii and Lactobacillus crispatus decreased and were found to be inversely related to Gardnerella vaginalis concentrations (p<0.001). Women with BV had a variety of fastidious bacteria whose concentrations dropped below detection thresholds 1-5 days after starting metronidazole. Recurrent BV was characterized by initial profound decreases of BV-associated bacteria after treatment followed by subsequent increases at relapse. The microbiota of the human vagina can be highly dynamic. Healthy women are colonized with Lactobacillus species, but levels can change dramatically over a month. Marked increases in G. vaginalis were observed during menses. Participants with BV have diverse communities of fastidious bacteria that are depleted by vaginal metronidazole therapy. Women with recurrent BV initially respond to antibiotic treatment with steep declines in bacterial concentrations, but these bacteria later reemerge, suggesting that antibiotic resistance in these bacteria is not an important factor mediating BV recurrence.

Bacterial vaginosis (BV), the overgrowth of diverse anaerobic bacteria in the vagina, is the most common cause of vaginal symptoms worldwide. BV frequently recurs after antibiotic therapy, and the best probiotic treatments only result in transient changes from BV-associated states to “optimal” communities dominated by a single species of Lactobacillus . Therefore, additional treatment strategies are needed to durably alter vaginal microbiota composition for patients with BV. Vaginal microbiota transplantation (VMT), the transfer of vaginal fluid from a healthy person with an optimal vaginal microbiota to a recipient with BV, has been proposed as one such alternative. However, VMT carries potential risks, necessitating strict safety precautions. Here, we present an FDA-approved donor screening protocol and detailed methodology for donation collection, storage, screening, and analysis of VMT material. We find that Lactobacillus viability is maintained for over six months in donated material stored at − 80 °C without glycerol or other cryoprotectants. We further show that species-specific quantitative PCR for L. crispatus and L. iners can be used as a rapid initial screening strategy to identify potential donors with optimal vaginal microbiomes. Together, this work lays the foundation for designing safe, reproducible trials of VMT as a treatment for BV.

We compared the effect of commercial vaginal douching products on Lactobacillus crispatus, L. jensenii, L. gasseri, L. iners , E. coli , and immortalized vaginal epithelial cells (VK2). All studied douching products (vinegar, iodine and baking soda based) induced epithelial cell death, and all inhibited growth of E. coli . Co-culture of vaginal epithelial cells with any of the lactobacilli immediately following exposure to douching products resulted in a trend to less human cell death. However, co-culture of epithelial cells with L. iners was associated with higher production of IL6 and IL8, and lower IL1RA regardless of presence or type of douching solution. Co-culture with L. crispatus or L. jensenii decreased IL6 production in the absence of douches, but increased IL6 production after exposure to vinegar. Douching products may be associated with epithelial disruption and inflammation, and may reduce the anti-inflammatory effects of beneficial lactobacilli.

The gut microbiota in patients with inflammatory bowel disease are perturbed in both composition and function. The vaginal microbiome and its role in the reproductive health of women with inflammatory bowel disease is less well described. We aim to compare the vaginal microbiota of women with inflammatory bowel disease to healthy controls. Women with inflammatory bowel disease enrolled in a longitudinal cohort study provided self-collected vaginal swabs. Healthy controls underwent provider-collected vaginal swabs at routine gynecologic exams. All participants completed surveys on health history, vulvovaginal symptoms and gastrointestinal symptoms, if applicable. Microbiota were characterized by sequencing the V4 region of the 16S rRNA gene. Associations between patient characteristics and microbial community composition were evaluated by PERMANOVA and Principal Components Analysis. Lactobacillus dominance of the microbial community was compared between groups using chi-square and Poisson regression. The cohort included 54 women with inflammatory bowel disease (25 Ulcerative colitis, 25 Crohn's Disease) and 26 controls. A majority, 72 (90%) were White; 17 (31%) with inflammatory bowel disease and 7 (27%) controls were postmenopausal. The composition of the vaginal microbiota did not vary significantly by diagnosis or severity of inflammatory bowel disease but did vary by menopausal status (p = 0.042). There were no significant differences in Shannon Diversity Index between healthy controls and women with IBD in premenopausal participants. There was no difference in proportion of Lactobacillus dominance according to diagnosis in premenopausal participants. A subgroup of postmenopausal women with Ulcerative colitis showed a significant higher alpha diversity and a lack of Lactobacillus dominance in the vaginal microbiome. Menopausal status had a larger impact on vaginal microbial communities than inflammatory bowel disease diagnosis or severity.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients. Therefore, samples from 20 premenopausal women with BV and treated with metronidazole were analyzed. Vaginal swabs, menstrual cup, and endocervical cytobrush samples were collected before treatment, weekly for four weeks, and at 2, 4, and 6 months for Nugent scoring, immune cell populations and cytokine analysis. Of 105 study intervals, 27 (25.7%) showed improvement in Nugent category, 61 (58.1%) remained unchanged, and 17 (16.2%) worsened. Improvement correlated with decreased monocytes ( p  = 0.005), while worsening was linked to increased monocytes ( p  < 0.001) and dendritic cells ( p  = 0.02). B cells ( p  = 0.02) and IFN-γ-induced chemokines - IP-10 ( p  = 0.007), MIG ( p  = 0.049), and ITAC ( p  = 0.005) - were associated with improvement. In conclusion, although the T-cell-associated chemokines IP-10, ITAC, and MIG were strongly associated with improvements in Nugent category, our findings indicate that antigen-presenting cells, particularly monocytes, show the most dynamic response to shifts in the vaginal microbiota in patients with BV.

The human vaginal microbiota is frequently dominated by lactobacilli and transition to a more diverse community of anaerobic microbes is associated with health risks. Glycogen released by lysed epithelial cells is believed to be an important nutrient source in the vagina. However, the mechanism by which vaginal bacteria metabolize glycogen is unclear, with evidence implicating both bacterial and human enzymes. Here we biochemically characterize six glycogen-degrading enzymes (GDEs), all of which are pullanases (PulA homologues), from vaginal bacteria that support the growth of amylase-deficient Lactobacillus crispatus on glycogen. We reveal variations in their pH tolerance, substrate preferences, breakdown products and susceptibility to inhibition. Analysis of vaginal microbiome datasets shows that these enzymes are expressed in all community state types. Finally, we confirm the presence and activity of bacterial and human GDEs in cervicovaginal fluid. This work establishes that bacterial GDEs can participate in the breakdown of glycogen, providing insight into metabolism that may shape the vaginal microbiota. Biochemical characterization of glycogen-degrading enzymes in vaginal bacteria reveals that the vaginal microbiota possesses the ability to metabolize glycogen in this environment.

Background Bacterial vaginosis (BV), the most common cause of vaginitis among reproductive age women, has high recurrence even after treatment. In addition to the physical risks of BV (e.g. increased HIV risk and adverse pregnancy outcomes such as preterm birth), the symptoms (malodour, itchiness, vaginal discharge) can cause emotional impacts (e.g. shame, embarrassment, self-consciousness). BV knowledge, attitudes, behavioural change(s) after diagnosis and other previous vaginal health concerns were explored among participants in a clinical trial assessing the safety and biologic effects of a vaginal live biotherapeutic product. Methods In-depth interviews (IDIs) were conducted with 37 female participants in a clinical trial in Boston, USA ( n  = 14), and Vulindlela, South Africa (SA) ( n  = 23). Interviews were audio recorded, transcribed and translated. Transcripts were coded and thematically analysed using NVivo. Results In this study, previous BV diagnosis was lower in SA than USA (2(9%) versus 12(86%)), with 7(19%) overall reporting a previous STI. There were five key themes: (1) Prior BV and other vaginal health experiences: Although BV was not frequently diagnosed in SA, participants reported experiencing symptoms (discharge, itchiness and malodour). Conversely, USA participants had experiences with previous BV diagnoses. (2) Previous vaginal health seeking behaviour and treatments: Almost all participants from both sites had sought treatment from healthcare professionals for vaginal health concerns, with a few from both sites having used self-care practices. (3) BV knowledge, attitudes and reactions to BV diagnosis: BV knowledge in SA was poor compared with the USA, but most participants were relieved to receive help. (4) Behavioural changes because of BV: Vaginal hygiene practices changed and participants washed more frequently/used products to address malodour. Further, BV symptoms resulted in changes in sex acts and/or abstinence. (5) BV diagnosis disclosure patterns: Disclosure varied, with participants commonly disclosing to those who could provide them with support. Conclusions BV knowledge, attitudes and experiences are related to previous diagnosis and treatment. Symptoms impact individuals’ behaviours regardless of previous diagnosis, and can have psychosocial impacts which need to be addressed via appropriate counselling and treatment strategies. Ongoing research for effective BV prevention and treatment options that can be made available and accessible to women with BV globally is needed. Trial registration South African National Clinical Trials Registry (SANCTR DOH-27-102023-8342; October 27, 2023) and ClinicalTrials.gov (NCT06135974; November 02, 2023).

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low Lactobacillus abundance are associated with a number of adverse reproductive outcomes, such as preterm birth, cervical dysplasia, and sexually transmitted infections (STIs), including HIV. Vaginal dysbiosis is associated with local mucosal inflammation, which likely serves as a biological mediator of poor reproductive outcomes. Yet the precise mechanisms of this FGT inflammation remain unclear. Studies in humans have been complicated by confounding demographic, behavioral, and clinical variables. Specifically, hormonal contraception is associated both with changes in the vaginal microbiome and with mucosal inflammation. In this study, we examined the transcriptional landscape of cervical cell populations in a cohort of South African women with differing vaginal microbial community types. We also investigate effects of reproductive hormones on the transcriptional profiles of cervical cells, focusing on the contraceptive depot medroxyprogesterone acetate (DMPA), the most common form of contraception in sub-Saharan Africa. We found that antigen presenting cells (APCs) are key mediators of microbiome associated FGT inflammation. We also found that DMPA is associated with significant transcriptional changes across multiple cell lineages, with some shared and some distinct pathways compared to the inflammatory signature seen with dysbiosis. These results highlight the importance of an integrated, systems-level approach to understanding host-microbe interactions, with an appreciation for important variables, such as reproductive hormones, in the complex system of the FGT mucosa.