Vaginal microbial communities or Community State Types
Unlike any other anatomical site of the human body, most vaginal microbial communities (>70%) are dominated by one or more species of Lactobacillus that constitute >50% of all genetic sequences obtained. Recent studies have shown that composition and relative abundance of vaginal microbial communities in reproductive-aged women cluster into at least five core vaginal microbiota, termed community state types (CSTs).1-3
Four of these CSTs, representing the majority (>70%) of women, are dominated by a different Lactobacillus species: L. crispatus (CSTI), L. gasseri (CSTII), L. jensenii (CSTV), and L. iners (CSTIII), whereas CSTIV is characterised by low proportions of lactobacilli and is composed of a diverse mixture of primarily strict anaerobic bacteria including species of the genera Gardnerella, Atopobium, Mobiluncus, Prevotella and other taxa in the order Clostridiales, as seen with states of Bacterial Vaginosis (BV).
Of note, L. iners is present in most women, including both healthy and those with dysbiosis/BV, whereas L. crispatus is typically only observed in healthy women. Ravel et al. observed that L. crispatus-dominated vaginal microbiota have lower vaginal pH compared to communities dominated by other species.1,4 Vaginal microbiotas dominated by L. iners have lower vaginal concentrations of D-lactic acid as L. iners lacks the gene coding for D-lactate dehydrogenase, so cannot produce this lactic acid isomer, which may in part mediate the higher observed frequency of BV and preterm delivery in these women.5,6
D-lactic acid levels were significantly higher when L. crispatus was the dominant vaginal bacterial species than when L. iners or Gardnerella dominated the vaginal microbiota.5 It has been suggested that the increased proportion of L. inersin women with BV may be due to increased tolerance of this Lactobacillus species to an elevated pH, characteristic of BV, more than other Lactobacillus species.7 In contrast, L. crispatus, L. gasseri, and L. jensenii are all producers of the D-lactic acid isomer as well as hydrogen peroxide.
L. iners also does not produce antimicrobial hydrogen peroxide. Hydrogen peroxide-producing lacto-bacilli are more likely to sustain long-term vaginal colonisation, and women colonised by hydrogen peroxide-producing lactobacilli have decreased acquisition of human immunodeficiency virus (HIV) infection, gonorrhoea, and BV.8,9 Evidence supports a vaginal microbiota dominated by Lactobacillus species other than L. iners is optimal to support vaginal health (i.e., strains of L. iners have not been considered candidates as probiotics to support women’s urogenital health).
Differences in the composition of these vaginal microbial communities have been observed between women of different ethnic backgrounds. Lactobacilli-dominated vaginal microbial communities (CST I, II, III, V) were observed in ~80% and ~90% of Asian and white women, respectively, but only ~60% and ~62% of Hispanic and black women, respectively.1 Over-representation of CSTIV in Hispanic and black women was associated with a higher median pH in these ethnic groups as well. Such differences in vaginal microbial communities between women of different ethnic backgrounds have been observed in other studies as well.3,12
Although CSTIV can be observed in otherwise healthy women, asymptomatic for BV, it is associated with higher Nugent scores (a Gram stain scoring system from 0-10 for vaginal swabs reflecting abundance of Gram-positive rods [lactobacilli] and Gram-negative variable rods and cocci [G. vaginalis, Prevotella, etc.] to diagnose BV with 0-3 considered normal, 4-6 indicative of intermediate bacterial counts, and 7-10 diagnostic of BV) and may be a risk factor for adverse gynaecologic and obstetric outcomes.13-15
REFERENCES 1. Ravel J, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011, 108 Suppl 1:4680-4687. 2. Gajer P, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 2012, 4:132ra152. 3. Zhou X, et al. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J 2007, 1:121-133. 4. Petrova MI, et al. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol 2015, 6:81. 5. Witkin SS, et al. Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: implications for protection against upper genital tract infections. MBio 2013, 4. 6. Petricevic L, et al. Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery. Sci Rep 2014, 4:5136. 7. Lamont RF, et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011, 118:533-549. 8. Martin HL, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 1999, 180:1863-1868. 9. Hawes SE, et al. Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J Infect Dis 1996, 174:1058-1063. 10. van de Wijgert JH, et al. The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One 2014, 9:e105998. 11. Bradshaw CS, Brotman RM. Making inroads into improving treatment of bacterial vaginosis – striving for long-term cure. BMC Infect Dis 2015, 15:292. 12. Fettweis JM, et al. Differences in vaginal microbiome in African American women versus women of European ancestry. Microbiology 2014, 160:2272-2282. 13. Lewis FM, et al. Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases. Obstet Gynecol 2017, 129:643-654. 14. Fredricks DN, et al. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005, 353:1899-1911. 15. Fox C, Eichelberger K. Maternal microbiome and pregnancy outcomes. Fertil Steril 2015, 104:1358-1363.
