Dysbiosis Of Vaginal Microbiota Research Articles

Vaginal microecology and its role in human papillomavirus infection and human papillomavirus associated cervical lesions.

The vaginal microecology comprises the vaginal microbiome, immune microenvironment, vaginal anatomy, and the cervicovaginal fluid, which is rich in metabolites, enzymes, and cytokines. Investigating its role in the female reproductive system holds paramount significance. The advent of next-generation sequencing enabled a more profound investigation into the structure of the vaginal microbial community in relation to the female reproductive system. Human papillomavirus infection is prevalent among women of reproductive age, and persistent oncogenic HPV infection is widely recognized as a factor associated with cervical cancer. Extensive previous research has demonstrated that dysbiosis of vaginal microbiota characterized by a reduction in Lactobacillus species, heightens susceptivity to HPV infection, consequently contributing to persistent HPV infection and the progression of cervical lesion. Likewise, HPV infection can exacerbate dysbiosis. This review aims to provide a comprehensive summary of current literatures and to elucidate potential mechanisms underlying the interaction between vaginal microecology and HPV infection, with the intention of offering valuable insights for future clinical interventions.

Effect of Lactobacillus delbrueckii subsp. lactis on vaginal radiotherapy for gynecological cancer

The aim of this study was to evaluate the effect of Lactobacillus delbrueckii subsp. lactis (L.del) on vaginal microbiota (VM) dysbiosis and vaginal radiation injury in gynecologic cancer patients. The inhibitory effects of L.del on cervical cancer cells were also studied in vitro. Gynecologic cancer patients receiving radiotherapy were randomized into control and L.del intervention groups. The control group received radiotherapy, while the intervention group received radiotherapy and L.del intervention (1 capsule/day placed into the deep vagina from the first day of radiotherapy until the end of treatment). Vaginal swab samples were collected on the first day pre-treatment and the last day post-treatment. DNA from 54 patients was extracted and assessed by the 16S rRNA sequencing method. Radiotherapy resulted in vaginal microbiome dysbiosis characterized by increased phylogenetic diversity and increased abundance of Brevundimonas, Streptococcus and Prevotella, but a decreased abundance of Lactobacillus. Level 2 vaginal radiation injury was positively associated with the abundance of Brevundimonas and gram-negative non-fermenting bacteria. Administration of L.del attenuated the reduction of Lactobacillus while also inhibiting the abundance of Streptococcus and Prevotella, thereby ameliorating radiotherapy-related vaginal microbiota dysbiosis. CLD inhibited the in vitro proliferation of SiHa cells by altering the expression of BCL2, HPV16-E6, HPV16-E7, IL6, MAP7, BAX, Caspase-3, Caspase-9 and LTF. In conclusion, L. del application can alleviate radiation-induced vaginal dysbiosis and restore Lactobacillus dominance of the vaginal microbiome. Moreover, CLD was found to inhibit cell growth and promote the apoptosis of SiHa cells in vitro. The registration number for this clinical trial is ChiCTR1900021784.

Lactobacillus Probiotics Improve Vaginal Dysbiosis in Asymptomatic Women.

Vaginal dysbiosis can lead to serious infections in asymptomatic women. Lactobacillus probiotics (LBPs) are being investigated as a promising therapy for reversing vaginal microbiota dysbiosis. This study aimed to investigate whether administering LBPs could improve vaginal dysbiosis and facilitate the colonization of Lactobacillus species in asymptomatic women. 36 asymptomatic women were classified based on the Nugent score as Low-NS (n = 26) and High-NS (n = 10) groups. A combination of Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, and Lactobacillus reuteri CBT LU4 was administered orally for 6 weeks. The study found that among women with a High-NS, 60% showed improved vaginal dysbiosis with a Low-NS after LBP intake, while four retained a High-NS. Among women with a Low-NS, 11.5 % switched to a High-NS. Genera associated with vaginal dysbiosis were positively correlated with the alpha diversity or NS, while a negative correlation was observed between Lactobacillus and the alpha diversity and with the NS. Vaginal dysbiosis in asymptomatic women with an HNS improved after 6 weeks of LBP intake, and qRT-PCR revealed the colonization of Lactobacillus spp. in the vagina. These results suggested that oral administration of this LBP could improve vaginal health in asymptomatic women with an HNS.

Synthetic bacterial consortia transplantation for the treatment of Gardnerella vaginalis-induced bacterial vaginosis in mice

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1β and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis.38ffAECrzJH4twA_o8BreEVideo

The evaluation of the Allplex™ BV molecular assay for the diagnosis of bacterial vaginosis in symptomatic South African females

Bacterial vaginosis (BV) is a dysbiosis of vaginal microbiota characterized by a shift from Lactobacillus species predomination to a heterogeneous mixture of anaerobes. We compared the performance characteristics of the Allplex ™ BV molecular assay with the reference test, Nugent score microscopy, for vaginal swab specimens from symptomatic South African women. A total of 213 patients were enrolled, of whom 99 (46.5%) and 132 (62.0%) were diagnosed with BV by Nugent and Allplex™, respectively. The Allplex™ BV assay displayed a sensitivity of 94.9% (95% CI, 88.7%−97.8%) and a specificity of 66.7% (95% CI, 57.6%−74.6%), with an agreement of 79.8% (95% CI, 73.9%−84.7%) (κ = 0.60). Assay design may be enhanced for improved specificity by accounting for differences in healthy and BV-associated vaginal microbiomes among women of different ethnicities.

Association between vaginal microbiota dysbiosis with asymptomatic UTI in pregnant woman and adverse pregnancy outcome- A case report

The vaginal microbiota dysbiosis [Bacterial vaginosis (BV)] is a condition in which the predominant Lactobacillus spp is replaced by anaerobic bacteria like and in the women of reproductive age group due to several factors. The women with BV are at a greater risk of acquiring urinary tract infection (UTI). The association of bacterial vaginosis and asymptomatic UTI in pregnant women pose risk for both mother and foetus. Here, a case of adverse pregnancy outcome in pregnant woman with BV and asymptomatic UTI is reported.

Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.

Vaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing. Vaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities. The microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study. These findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.

Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination.

Dysbiosis of vaginal microbiota is associated with increased HIV‐1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV‐1 infection via autophagy‐mediated degradation of HIV‐1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis‐associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV‐1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV‐1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis‐exposed LCs efficiently transmitted HIV‐1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV‐1 variants that establish infection after sexual transmission, the so‐called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV‐1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV‐1 infection.

Age-Stratified Analysis of Vaginal Microbiota Dysbiosis and the Relationship with HPV Viral Load in HPV-Positive Women.

Objective This study evaluated the distribution of vaginal microbiota dysbiosis and the association with HPV viral load test in high-risk HPV-positive women before and after 50 years old. Methods For this cross-sectional study, 388 HPV-positive women prior to referral to colposcopy in Peking University Peoples' Hospital were included and classified as younger than 50 years (n = 307) and aged 50 years or older (n = 81), midvagina bacterial community composition was characterized by FlashDetect™ MAX vaginal microbe detection kit, and BMRT-HPV reported type-specific viral loads/10,000 cells. Results The community state type (CST) IV was the most common CST occurring in 148 women (38.1%). The proportion of CST IV in those aged 50 years or older was significantly higher than those younger than 50 years (women) (66.7% vs. 30.6%); the difference was statistically significant (<0.001). CST distribution has no statistical difference in different grades of cervical lesion, regardless of the age (p = 0.238 and 0.263). However, the women with high-grade cervical lesion presented a more complicated trend and the abundance of vaginal microbiota dysbiosis than low-grade lesion. HPV16/18 viral load was found to be significantly higher in CST III and CST IV than CST I/II/V (p < 0.05)in women younger than 50 years. Conclusions In women younger than 50 years, higher HPV16/18 load was more closely associated with CST IV; however, it had no significant correlation in women aged 50 years or older.

Mycobiome Dysbiosis in Women with Intrauterine Adhesions.

ABSTRACTThe vaginal microbiota dysbiosis is closely associated with the development of reproductive diseases. However, the contribution of mycobiome to intrauterine adhesion (IUA) disease remains unknown. Harnessing 16S and ITS2 rDNA sequencing analysis, we investigate both bacterial and fungal microbiota compositions across 174 samples taken from both cervical canal (CC) and middle vagina (MV) sites of IUA patients. Overall, there is no significant difference in microbial diversity between healthy subjects (HS) and IUA patients. However, we observe the IUA-specific bacterial alterations such as increased Dialister and decreased Bifidobacterium and enriched fungal genera like increased Filobasidium and Exophiala. Moreover, site-specific fungal-bacterial correlation networks are discovered in both CC and MV samples of IUA patients. Mechanistic investigation shows that Candida parapsilosis, other than Candida albicans and Candida maltosa, prevents the exacerbation of inflammatory activities and fibrosis, and modulates bacterial microbiota during IUA progression in a rat model of IUA. Our study thus highlights the importance of mycobiota in IUA progression, which may facilitate the development of therapeutic target for IUA prevention.IMPORTANCE Intrauterine adhesion (IUA) often leads to hypomenorrhea, amenorrhea, repeat miscarriages, and infertility. It has been prevalent over the last few decades in up to 13% of women who experience pregnancy termination during the first trimester, and 30% of women undergo dilation and curettage after a late, spontaneous abortion. However, the pathogenesis of IUA remains unclear. Despite reports of microbiota dysbiosis during IUA progression, there is little information on the effect of fungal microbiota on the development of IUA. This study not only enhances our understanding of the mycobiome in IUA patients but also provides potential intervention strategies for prevention of IUA by targeting mycobiome.

HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources

Despite the high prevalence of both cervico-vaginal human papillomavirus (HPV) infection and bacterial vaginosis (BV) worldwide, their causal relationship remains unclear. While BV has been presumed to be a risk factor for HPV acquisition and related carcinogenesis for a long time, here, supported by both a large retrospective follow-up study (n = 6,085) and extensive in vivo data using the K14-HPV16 transgenic mouse model, we report a novel blueprint in which the opposite association also exists. Mechanistically, by interacting with several core members (NEMO, CK1 and β-TrCP) of both NF-κB and Wnt/β-catenin signaling pathways, we show that HPV E7 oncoprotein greatly inhibits host defense peptide expression. Physiologically secreted by the squamous mucosa lining the lower female genital tract, we demonstrate that some of these latter are fundamental factors governing host-microbial interactions. More specifically, several innate molecules down-regulated in case of HPV infection are hydrolyzed, internalized and used by the predominant Lactobacillus species as amino acid source sustaining their growth/survival. Collectively, this study reveals a new viral immune evasion strategy which, by its persistent/negative impact on lactic acid bacteria, ultimately causes the dysbiosis of vaginal microbiota.

Dysbiosis of vaginal microbiota associated with persistent high-risk human papilloma virus infection

BackgroundThe status of vaginal microbiota in persistent high-risk human papilloma virus (HR-HPV) infection is unclear. The present work aimed to identify the vaginal microbiota of persistent HPV infection and explore the possible underlying microbiota factors.MethodsA total of 100 women were recruited in this study, of which 28 presented HR-HPV persistent infection (P group), 30 showed clearance of any subtype of HR-HPV (C group), and 42 had no history of any HR-HPV infection (NC group). The vaginal microbiota and the community structure of the three groups were compared based on the 16S rRNA sequencing of the V3–V4 region. The microbiota diversity and differential analysis were carried out to detect the potential factors associated with HR-HPV infection.ResultsP and C groups showed an increase of Firmicutes and Actinobacteriota but a decrease in Proteobacteria compared to the NC group. The Chao1 index indicated that the microbial richness of the NC group was greater than C group (P < 0.05).The principal co-ordinate analysis(PCoA) revealed differences between the NC and P/C groups.The linear discriminant analysis effect size (LEfSe) method indicated that Proteobacteria phylum was significantly different in the mean relative abundance in the NC group,but the P and C groups did not show such indicative taxa. The Wilcox rank-sum test indicated that the Bifidobacterium (P = 0.002) and Lactobacillus (P = 0.005) of the C group were in a high mean relative abundance compared to the NC group.ConclusionsThe persistent HR-HPV infection is associated with dysbiosis of the vaginal microbiota. Microbiome regulation with Bifidobacteria and Lactobacillus may affect the clearance of HPV.

Экофуцин® как профилактика развития кандидозно- бактериального дисбиоза влагалища на фоне применения системной антибактериальной терапии

Aim: to assess the efficacy and safety of Ecofucin® in patients after performing planned gynecologic surgery procedures based on the changes in vaginal microbiota over time amid the use of systemic antimicrobial therapy (AMT). Patients and Methods: this prospective open randomized comparative parallel-group clinical study involved patients without signs of vaginal microbiota dysbiosis — bacterial vaginosis or candidiasis, who were hospitalized for planned surgery procedures. The group 1 patients (n=39) received systemic AMT and Ecofucin® for intravaginal application once a day at the bedtime for 12 days, starting 6 days before the planned surgery and AMT initiation, while the group 2 patients (n=40) received only systemic AMT. The efficacy was assessed a day after the completion of AMT and the use of the tested medication (i.e. on day 13 after the initiation of Ecofucin application) and 30±2 days after the initiation of using the tested drug. Clinical, microbiological and molecular genetic methods were used for the assessment. Results: symptoms common for vaginal microbiota dysbiosis — bacterial vaginosis and candidiasis were reported by 18% and 21% of the group 2 patients at days 13 and 30±2 after the initiation of AMT, while such symptoms were not recorded in any of the group 1 patients (F=0,107, р=0,007). In 100% of the group 1 patients both lactobacilli and bifidobacteria were detected at all endpoints. In group 2, lactobacilli were found at days 13 and 30±2 in 93.8% and 97% of patients, respectively (F=0.035, p=0.2; F=0.017, p=0.458), bifidobacteria — in 84.4% and 81.1% of patients, respectively (F=0.092, р=0.016; F=0.107, р=0,007, respectively). At the baseline, the groups had similar results of the vaginal discharge culture tests. In the group 1 patients, Candida spp. were not identified at any of the endpoints, in group 2 — Candida spp. were found in 22.5% of patients, starting from day 13 (F=0,125, р=0,002). No adverse events were reported. Conclusion: the administration of Ecofucin® vaginal suppositories containing natamycin 100 mg and excipient lactulose is effective for preventing microbiota dysbiosis — bacterial vaginosis and candidiasis in patients receiving antimicrobial therapy. KEYWORDS: vagina, microbiocenosis, antimicrobial therapy, lactobacilli, bifidobacteria, candidiasis, natamycin, lactulose. FOR CITATION: Kuzmin V.N. Ecofucin® for the prevention of vaginal microbiota dysbiosis — bacterial vaginosis and candidiasis amid the use of systemic antimicrobial therapy. Russian Journal of Woman and Child Health. 2022;5(4):292–296 (in Russ.). DOI: 10.32364/2618-8430- 2022-5-4-292-296.

Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.

Role of Vaginal Microbiota Dysbiosis in Gynecological Diseases and the Potential Interventions.

Vaginal microbiota dysbiosis, characterized by the loss of Lactobacillus dominance and increase of microbial diversity, is closely related to gynecological diseases; thus, intervention on microbiota composition is significant and promising in the treatment of gynecological diseases. Currently, antibiotics and/or probiotics are the mainstay of treatment, which show favorable therapeutic effects but also bring problems such as drug resistance and high recurrence. In this review, we discuss the role of vaginal microbiota dysbiosis in various gynecological infectious and non-infectious diseases, as well as the current and potential interventions.

Alteration of vaginal microbiota in patients with recurrent miscarriage

The aim of this study was to characterise the structure of vaginal microbiota in unexplained recurrent miscarriage (RM). The vaginal bacterial communities of 16 patients with RM and 20 healthy volunteers were sampled. Then, the microbiomes of bacterial profiles of RM patients and healthy volunteers were compared by sequencing the V3–V4 regions of the bacterial 16S ribosomal RNA gene using the Illumina MiSeq platform (Illumina, San Diego, CA). Taxonomic analysis demonstrated that abundance of Lactobacillus and Gardnerella were significantly different between the RM and control groups. Furthermore, at the genus level, Lactobacillus was the most dominant genus in the two groups. Statistically significant differences were observed in three genera between RM and control groups. In the control group, two bacterial taxa were significantly more abundant (Lactobacillus and Gardnerella), while only one taxon was overrepresented in the RM group (Atopobium). These present findings provide experimental evidence supporting vaginal microbiota dysbiosis in women with RM. Impact statement What is already known on this subject? Currently, bacterial vaginosis is thought to be mainly due to the vaginal dysbacteriosis, which can induce unexplained recurrent miscarriage, premature rupture of membranes, low birth weight premature birth, premature birth, chorioamnionitis and series of diseases. What do the results of this study add? The current study demonstrated that Lactobacillus and Gardnerella were significantly decreased in RM patients compared to healthy control, while Atopobium was overrepresented in the RM group. What are the implications of these findings for clinical practice and/or further research? Clinically, women with RM might benefit from vaginal microbiota treatment, adjuvant therapy with Lactobacillus-based live biotherapeutics.

Potential Association between Vaginal Microbiota and Cervical Carcinogenesis in Korean Women: A Cohort Study.

Convincing studies demonstrated that vaginal flora is one of the most impactful key components for the well-being of the genital tract in women. Nevertheless, the potential capability of vaginal-derived bacterial communities as biomarkers to monitor cervical carcinogenesis (CC) has yet to be studied actively compared to those of bacterial vaginosis (BV). We hypothesized that vaginal microbiota might be associated with the progression of CC. In this study, we enrolled 23 participants, including healthy controls (HC group; n = 7), patients with cervical intraepithelial neoplasia (CIN) 2 and 3 (CIN group, n = 8), and patients with invasive cervical cancer (CAN group; n = 8). Amplicon sequencing was performed using the Ion Torrent PGM to characterize the vaginal microbiota. Patients with CIN and CAN presented vaginal microbiota dysbiosis compared with HC. The alpha diversity analysis revealed that CC has a trend to be increased in terms of diversity indexes. Moreover, CC was associated with the abundance of specific microbes, of which Lactobacillus and Gardnerella were the most significantly different between HC and CIN, whereas Streptococcus was differentially abundant in CAN compared with CIN. We then evaluated their diagnostic abilities. Testing in terms of diagnostic ability using the three genera revealed considerably high performance with an area under the receiver-operating characteristic curve of 0.982, 0.953, and 0.922. The current study suggests that the presence of Gardnerella and Streptococcus may be involved in the advancment of CC.

Role of Lactobacillus in Female Infertility Via Modulating Sperm Agglutination and Immobilization.

Infertility has become a common problem in recent decades. The pathogenesis of infertility is variable, but microbiological factors account for a large proportion of it. Dysbiosis of vaginal microbiota is reportedly associated with female infertility, but the influence of normal vaginal microbiota on infertility is unclear. In this review, we summarize the physiological characteristics of the vaginal tract and vaginal microbiota communities. We mainly focus on the bacterial adherence of vaginal Lactobacillus species. Given that the adherent effect plays a crucial role in the colonization of bacteria, we hypothesize that the adherent effect of vaginal Lactobacillus may also influence the fertility of the host. We also analyze the agglutination and immobilization effects of other bacteria, especially Escherichia coli, on ejaculated spermatozoa, and speculate on the possible effects of normal vaginal microbiota on female fertility.

Vaginal Microbial Community Dysbiosis and Associated Outcomes among Women under Contraception at Musasa Health Center, Rwanda

Background: Vaginal microbiota dysbiosis could lead to the vaginal health conditions. This imbalance in vaginal microbiota can be due to a number of factors including contraceptive methods. Objective: This study was carrried out to investigate the vaginal microbiota dysbiosis and associated vaginal health outcomes among women under contraception at Musasa health Center. Materials and Methods: This was a cross sectional study. 56 vaginal swab samples were collected from women enrolled in a family planning program, and transported to INES Ruhengeri clinical microbiology laboratory for vaginal microbial community analysis. The outcomes were evaluated by scheduled interviews. Chi square test was used to evaluate association of microbiota imbalances in the vagina and the vaginal health outcomes. Results: Lactobacilli (92.85%) was the most predominant microorganism observed in the vagina. Outcomes of the vaginal microbiota dysbiosis under different contraceptive regimes were observed. Vaginal microbial community imbalance in different family planning methods was statistically significant (x2 = 36.5, P = 0.049048) to be associated with vaginal health outcomes such as bacterial vaginosis, urinary tract infections, candidiasis and vaginitis. The association with contraceptives contraceptive methods and vaginal microbial community dysbiosis was statistically significant (x2 = 96.2403, P = 0.000491). The Implant for 5 years and Intrauterine device (IUD) were statistically significant (x2 = 28.533, P = 0.002681 and x2 = 27, P = 0.004595 respectively) to contribute to the vaginal microbiota balance. Conclusion: This study established that family planning methods could cause vaginal dysbiosis thereby exposing the vagina to adverse health outcomes and poor reproductive health. Women undergoing family planning should seek medical support if any sign of vaginal infection is observed.

In silico trio-biomarkers for bacterial vaginosis revealed by species dominance network analysis.

BV (bacterial vaginosis) influences 20%-40% of women but its etiology is still poorly understood. An open question about the BV is which of the hundreds of bacteria found in the human vaginal microbiome (HVM) are the major force driving the vaginal microbiota dysbiosis. Here, we recast the question of microbial causality of BV by asking if there are any prevalent 'signatures' (network motifs) in the vaginal microbiome networks associated with it? We apply a new framework [species dominance network analysis by Ma & Ellison (2019): Ecological Monographs) to detect critical structures in HVM networks associated with BV risks and etiology. We reanalyzed the 16s-rRNA gene sequencing datasets of a mixed-cohort of 25 BV patients and healthy women. In these datasets, we detected 15 trio-motifs that occurred exclusively in BV patients. We failed to find any of these 15 trio-motifs in three additional cohorts of 1535 healthy women. Most member-species of the 15 trio motifs are BV-associated anaerobic bacteria (BVAB), Ravel's community-state type indicators, or the most dominant species; virtually all species interactions in these trios are high-salience skeletons, suggesting that those trios are strongly connected 'cults' associated with the occurrence of BV. The presence of the trio motifs unique to BV may act as indicators for its personalized diagnosis and could help elucidate a more mechanistic interpretation of its risks and etiology. We caution that scarcity of large longitudinal datasets of HVM also limited further verifications of our findings, and these findings require further clinical tests to launch their applications.