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Table 1 Human vaginal microbiome study across the world (2007–2020) and its main findings

From: Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

Country/place Research design Main findings References
Tienen, Belgium 26 women: 11 healthy, 5 BV, 7 VVC, and 3 BV-VVC
Age: 23–40
Cross-sectional study
Microbial profiling by using PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR analysis for 16S rRNA
PCR-DGGE revealed vaginal microbiota is stable over time in healthy women which dominated by L. acidophilus, L. gasseri, L. iners, L. vaginalis
Low number of G. vaginalis co-exist with Lactobacillus in some healthy women which may acts as sentinel species and are susceptible to environmental, biological, and physical changes
Low abundance of lactobacilli was reported in BV patients, concomitantly with an increase of BVAB such G. vaginalis, A. vaginae, Leptotrichia, Megasphaera, Prevotella, Staphylococcus, Streptococcus, Veillonella
An increased of non-H2O2-producing L. iners and decreased of L. acidophilus, L. gasseri, L. vaginalis abundance in VVC patients
[264]
Iowa, USA Cross-sectional study
42 women: 21 healthy and 21 RVVC-infected women (≥ 4 times in 2 years)
Age: 18–40
Microbial profiling by using 16S rRNA terminal restriction fragment polymorphisms (T-RFLP)
No significant difference in bacteria communities and vaginal pH were reported among VVC-infected and healthy women
Most RVVC patients were not symptomatic
No correlation between vaginal communities and risk of RVVC was reported
[265]
Georgia and Maryland, USA Cross-sectional study
396 non-pregnant women
Age: 12–45
Microbial profiling by using barcoded 16S rRNA sequencing
Introduction of five vaginal CSTs (I, II, III, IV, V) to profile vaginal microbiota status based on lactobacilli abundance
Higher vaginal pH (pH 4.7–5.5) has been reported for Black and Hispanic women in respect to Asian and White women (pH 4.2–4.4)
Vaginal CST III (L. iners-dominated) and CST IV (BVAB-dominated) were more frequently reported in Black and Hispanic women
[10]
China 95 non-pregnant women: 30 healthy, 39 VVC, 16 BV-VVC, 10 BV
Cross-sectional study
Microbial profiling by using barcoded 16S rRNA sequencing
Lactobacillus-dominated vaginal microbiota is reported in healthy China women, with acidic vaginal pH (< pH 4.5)
BV-infected women showed the highest diversity of vaginal microbiota (low abundance of Lactobacillus)
BV-VVC women with a unique pattern of higher abundance of Lactobacillus
Wide variety of vaginal microbiota reported in VVC-only women and showed unusual microbiota profile such as Streptococcus-dominated and Gardnerella-dominated microbiota after azole treatment
BV-VVC women showed an increased abundance of Lactobacillus after antimicrobial treatment
[266]
Estonia 494 healthy and asymptomatic Caucasian women
Age: 15–44
Cross-sectional study
Bacterial profiling by barcoded 16S rRNA and fungal profiling by ITS sequencing
Lactobacillus-dominated vaginal microbiota reported in healthy and asymptomatic women
BVAB such as A. vaginae and G. vaginalis is also reported in some women which can be classified as asymptomatic BV-infected women
The diversity of vaginal microbiota increased with higher vaginal pH and malodorous discharge were present in women
Candida species especially Candida albicans remains the most common yeast isolated from asymptomatic women
[39]
Seattle, USA 45 women enrolled in longitudinal study (2007–2010)
Treatment with metronidazole for 7, 14, 21, 28 days
Microbial profiling by using qPCR of 16S rRNA and bacterial dynamic analysis by mathematical modelling
Rapid reduction of BVAB within first day of treatment and gradual increment in L. iners abundance during the transient vacuum period
The treatment is not effective against G. vaginalis and recurrence of BV is frequently reported in the patients
[267]
Toronto, Canada 182 pregnant women (11–16 weeks of gestation)
Microbial profiles were compared with previous study non-pregnant Canada women (n = 310)
Microbial profiling by using universal primer cpn60 sequencing
Pregnant women with Lactobacillus-dominated CST has relatively higher abundance of lactobacilli as compared to non-pregnant women
Lower richness and diversity (low abundance of Mollicutes and Ureaplasma) are reported in pregnant woman associated with low risk of preterm birth and pregnancy loss
Hormone-induced glycogen production may provide conducive environment for bacterial growth in vagina explained pregnant women carried higher bacterial load as compared to non-pregnant women
[268]
Kenya, South Africa, Rwanda (Three sites) 80 women from Vaginal Biomarkers Study: 40 healthy and 40 BV
8 weeks longitudinal study (five consecutive visits)
Gram-staining, qPCR, quantification of soluble immune mediators in cervicovaginal lavages
Total of 79% of the women with Lactobacillus crispatus-dominated microbiota are accompanied by Lactobacillus vaginalis whereas L. jensenii and L. gasseri are not present in the women
Healthy women (normal Nugent score) has L. iners-dominated microbiota and is significantly associated with microbiota diversity and vaginal inflammation due to sexual activity and amenorrhoea
BV-infected women (Nugent 7–10) reported low lactobacilli and high G. vaginalis, A. vaginae, and P. bivia abundance accompanied by the increased of proinflammatory cytokines (IL-1β, IL-12) and decreased of antiprotease elafin (IP-10)
[269]
University of Maryland, USA 40 non-pregnant women
Cross-sectional study
Microbial profiling by 16S rRNA sequencing
Vaginolysin (cytototoxic protein) quantification
Higher concentration of vaginolysin was reported in CST-IV as compared to high abundance of CST-I microbiota
Intermediate concentration of vaginolysin has been reported in L. iners-dominated microbiota (CST-III) women
Higher abundance of G. vaginalis has been reported in lactobacilli-deficient vaginal microbiota and associated with increasing vaginal pH, Nugent score, and vaginolysin concentration
[270]
Istanbul, Turkey 28 healthy Caucasian women: 14 histologic-endometriosis and 14 healthy
Prospective observational cohort study
Microbial profiling by using 16S rRNA metagenomic sequencing
Lactobacilli remain the dominant genus in healthy and endometriosis-diagnosed women
The abundance of G. vaginalis is significantly higher in endometriosis-diagnosed as compared to healthy women
The absence of A. vaginae in vagina and cervix, increased of E. coli, Shigella, Streptococcus, and Ureaplasma abundance in cervix were reported in women with endometriosis
[271]
Centre for Health Behaviour Research, University of Maryland School of Public Health, USA 39 women: 26 HPV-positive (14 high-risk HPV) and 13 HPV-negative
Cross-sectional study
Microbial profiling by using 16S rRNA sequencing and vaginal metabolites profiling by using liquid chromatograph mass spectrometry
HPV-positive women were reported of having a higher biogenic amines (i.e. putrescine and ethanolamine) concentration and lower glutathione (GSH), glycogen, and phospholipid concentration compared to HPV-negative women
Higher concentration of biogenic amines and glycogen-related metabolites were also reported in HPV-positive women (CST-III vaginal microbiota)
Higher concentration of GSH, glycogen, and phospholipid-related metabolites have been reported in HPV-positive women (CST-IV vaginal microbiota)
HPV-positive women had lower concentration of amines, lipids, and peptides as compared to HPV-negative women across all vaginal microbiota state
Oxidative stress environments in vagina created from high level of biogenic amines and GSH may compromise host response against infection
[272]
Bologna, Italy 79 women: 21 healthy, 20 BV-, 20 CT-, 18 VVC-infected women
Cross-sectional study
Microbial profiling by using 16S rRNA MiSeq sequencing and metabolomic analysis by 1H-NMR
Vaginal microbiota in healthy women are dominated by L. crispatus
Low abundance of Lactobacillus and high abundance of A. vaginae, Faecalibacterium, Megasphaera, Roseburia observed in CT-infected women
Low abundance of Lactobacillus and high abundance of BVAB were reported in BV- and VVC-infected women
Reduction of dimethylamine and increment of trimethylamine level in vaginal dysbiosis conditions (BV, VVC, CT)
Production of lactic acid and branched-chain amino acids (i.e. valine, leucin, isoleucine) are higher in healthy women
Increment of biogenic amines and short-chain organic acids were reported in BV-infected women
Higher glucose level was reported in VVC-infected women, may decrease the abundance of L. crispatus and promote the virulence of Candida
[24]
Missouri (St. Louis), USA 255 women: 42 Candida-colonised and 213 non-Candida colonised
Inclusion of Black and White women with normal, intermediate, and BV-type vaginal microbiota
Nested cross-sectional study
Microbial profiling by using qPCR of 16S rRNA
Inhibition assay of lactobacilli against Candida in vitro growth
A total of 20% (52/255), 39% (99/255), and 38% (98/255) women reported L. crispatus-, L. iners-, and non-Lactobacillus dominated vaginal microbiota, respectively
Lactobacillus iners-dominated vaginal microbiota is more likely to have Candida colonisation as compared to L. crispatus-dominated vaginal microbiota
Cell-free supernatant from L. crispatus having lower pH (higher level of protonated lactic acid) and are correspondingly more effective to inhibit Candida colonisation as compared to L. iners
[273]
Kigali, Rwanda 68 high-risk BV or TV patients: only 55 actively sought for treatment
Subjects treated with 7 days of 500 mg oral metronidazole
Microbial profiling by using 16S rRNA HiSeq sequencing and BactQuant 16S gene quantitative PCR
The cure rate of BV after metronidazole treatment only achieved 54.5%
Modest reduction in the abundance of BV-anaerobes after treatment (16.4% of total patients have reduction of 50% BV-population)
Overall abundance of lactobacilli increased with L. iners recorded the highest abundance after treatment (success and failure)
The presence of high abundance of pathobionts and G. vaginalis in women associated with likelihood of treatment failure potentially due to biofilm formation
[274]
  1. BV: bacterial vaginosis; CT: Chlamydia trachomatis; RVVC: recurrent vulvovaginal candidiasis; VVC: vulvovaginal candidiasis; TV: Trichomonas vaginalis; BV-VVC: co-infection of BV and VVC; BVAB: BV-associated bacteria; CSTs: community state types; IP-10: Interferon-γ induced protein-10 (chemokine); ITS: Internal transcribed spacer; OTUs: Operational taxonomic units; PTB: Preterm birth; T1D: Type-I diabetes