Vaginal Microbiota

This article is an extract from the PDF “The Vaginal Microbiota”, available as a free download.

The debate about the relevance and existence of bacteria populating the vaginal tract dates back to 1870. The main question revolved around the origin of puerperal sepses (sepses during delivery): are they due to external contamination such as doctors’ or midwives’ hands for example, or to an infectious agent already present in normal conditions in the vagina or uterus of pregnant women?

In 1887, the observation under the microscope of the vaginal secretions of pregnant women led Gönner to mention the presence of pyogenic organisms (Staphylococcus, Streptococcus) and a multitude of bacteria which were nevertheless not culturable.

Döderlein on the other hand, observed that urine samples were sterile but that vaginal secretions contained pyogenic cocci. He firmly concluded that self-infection of pregnant women was the explanation to puerperal sepses.

In 1892, Döderlein published a monograph titled “Das Scheidensekret” (vaginal secretion) which reported the bacteriological study of the vaginal secretions of nearly 200 women. This work supported his theory of self-infection, but its main significance lay in the description and images of vaginal bacilli named Döderlein bacilli, later named Lactobacillus acidophilus in 1928.

Döderlein separated the bacterial communities of pregnant women into 2 categories:

–          normal bacterial communities dominated by vaginal bacilli

–          abnormal bacterial communities dominated by streptococci and staphylococci

He supported the theory according to which the vaginal lactobacilli contained in normal vaginal secretions maintain an acidity which protects the vagina against pathogenic bacteria [RAMPERSAUD 2012].

Years later, it turned out that other facultative or obligate anaerobic bacteria as well as yeast were also present in the vagina, but in smaller numbers than the lactobacilli. In addition, L. acidophilus is not a single species but a complex made up of very similar species. DNA homolgy studies separated this complex into L. jensenii, L. casei, L. gasseri, L. crispatus, L. plantarum, L. fermentum, L. cellobiosus, L. brevis, L. minutus and L. salivarius. It is interesting to note that L. minutus was reclassified to novel genus Atopobium in 1992 and named Atopobium minutum  [HICKEY 2012].

Over 120 Lactobacillus species have been documented across the world, yet just over 20 species have been detected in the vaginal region.

Molecular biology techniques have shown that the vaginal flora of healthy women does not contain a large number of different lactic species but at most 1 to 2 species from L. crispatus, L. iners, L. jensenii and L. gasseri. The other species are rare, their abundance low and they seem to belong to novel phylotypes [LAMONT 2011].

From birth to menopause

The vaginal ecosystem at birth and during early childhood

Shortly after birth, the newborn’s vaginal epithelium is rich in glycogen due to the maternal oestrogen supply, thus creating a favourable environment for the development of lactic bacteria. The vaginal pH is neutral or slightly alkaline.

Due to the absence of gonadic and adrenal hormones and a drop of available oestrogen, the prevalence of lactic acid-producing bacteria reduces [HAN 2009] . The neutral or slightly alkaline vaginal pH vaginal of early childhood promotes the development of aerobic and facultative anaerobic bacteria [SHAFER 1985].

The vaginal flora of post-menarche adolescents

In parallel to adrenal and gonadic maturation, hormonal cycles are established and menstruation start. The oestrogen produced at mid-cycle induces the formation of glycogen peaks in the vaginal epithelium which promote the development of lactic acid-producing bacteria.

The vaginal microbiota of women of childbearing age

396 women of childbearing age, who did not present with any symptoms of vaginal disease and were sexually active, were recruited for a study whose aims were to:

–  establish a correlation or not between the composition of certain vaginal bacterial communities and vaginal pH in order to highlight their performance or participation in maintaining good vaginal health

–   establish a correlation or not between the composition of certain vaginal bacterial communities and Nugent score

–    evaluate the relative abundance of certain bacterial species which could reflect an antagonism or interaction between the different species.

Overall, it was observed that all bacterial communities had members who synthesised lactic acid such as Lactobacillus, Megasphaera, Streptococcus or Atopobium for example; this would suggest that lactic acid production is maintained in all communities despite their differing bacterial compositions.

Vaginal microbiota variations during menstrual cycles

   The temporal dynamism of vaginal microbial communities was evaluated from                 32 healthy women of childbearing age. To that end, vaginal samples were taken                 twice/week over a 16-week period.

  The study showed that in some women the vaginal bacterial communities evolved      significantly in a very short lapse of time, whereas for other women, it remained    relatively stable even in those women with Lactobacillus sp.-poor bacterial    communities.

  Menstruation had a significant negative impact on microbiota stability, as did sexual relations. Nevertheless, these fluctuations did not automatically lead to a loss of performance of the microbiota, for example in relation to lactic acid production, which is covered by other members of the community. It is therefore reasonable to assume that susceptibility to disease would occur during vaginal microbiota fluctuations.         [GAJER 2012].

Vaginal microbiota of healthy women of childbearing age, of intermediate stage or presenting with bacterial vaginosis

The study conducted by SHIPITSYNA E. et al. aimed to evaluate in detail the vaginal microbiota of healthy women and women with bacterial vaginosis, with the view of determining discriminating bacterial species for diagnosing the disease.

Great differences in the distribution of genera and bacterial species were observed in the 3 groups.

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  • Control group (n=79)

– The healthy women had a vaginal microbiota dominated by Lactobacillus spp. estimated at approximately 90% of analysed sequences;

– L. iners and L. crispatus were predominant over other lactobacilli

  • Intermediate group (n=11)

– L. iners and G. vaginalis were predominant over all other species and were estimated at almost 75% of analysed sequences.

  • Group presenting with bacterial vaginosis (n=73)

The vaginal microbiota of these women contained a wide variety of bacterial species:

– G. vaginalis (29.1% of sequences)

– Prevotella (13.2%)

– Megasphaera type 1 (10%)

– A. vaginae (7.1%)

– L. amnionii (6.8%)

– L. iners (6.6%)

– BVAB1 (6.1%)

– BVAB2 (6.3%)

– S. sanguinegens (4.3%)

– Eggerthella (1.2%)

Vaginal microbiota of post-menopausal women

Menopause is characterised by reduced oestrogen production resulting in vaginal dryness and vaginal epithelium atrophy.

When oestrogen levels drop, glycogen levels also drop; leading to reduced lactobacilli and increased vaginal pH as glucose is no longer converted into lactic acid.

In a study evaluating the vaginal health of 921 women aged 40 years or more using vaginal smear staining and observation under the microscope, only 46.3% of post-menopausal women not undergoing hormone treatment (273/590) had a normal, Lactobacillus-rich vaginal flora as determined by the Nugent score (score between 0 and 3) [CAUCI 2002].

Menopause and vaginal dryness: vaginal microbiota involvement

HUMMELEN R. et al. (12) conducted a clinical study with a dual aim:
–       to characterise the vaginal microbiota of post-menopausal women in good vaginal health compared to those suffering from vaginal dryness
–       to examine the differences in vaginal epithelium gene expression between these 2 communities

119 OTU (Operational Taxonomic Units) were detected, each corresponding to a bacterial taxon.
The microbiota of the healthy women (no vaginal dryness or low vaginal dryness) had low bacterial diversity and was dominated by lactobacilli belonging to the L. iners and L. crispatus species.

In contrast, the microbiota of the women suffering from moderate to severe vaginal dryness had a lower Lactobacillus abundance and high bacterial diversity. Their vaginal microbiota were rich in Prevotella timonensis (OTU_6), Porphyromonas (OTU_9), Peptoniphilus (OTU_27) and Bacillus (OTU_34). In addition, Lactobacillus ratios and vaginal dryness severity were inversely correlated.

References 

CAUCI S., DRIUSSI S., De SANTOS D., PENACCHIONI P., IANNICELLI T., LANZAFAMME P., De SETA F., QUADRIFOGLIO F., De ALOYSIO D. & GHASCHINO S. Prevalence of bacterial vaginosis and vaginal flora changes in peri-and postmenopausal women Journal of Clinical Microbiology, 2002, 40, 6, 2147-2152.
GAJER P. et al. Temporal dynamics of the human vaginal microbiota. Sci Transl. Med., 2012, 4 (132):132ra52 Doi: 10.1126/scitranslmed. 3003605.
HAN Y.W., SHEN T., CHUNG P., BUHIMSCHI I.A. & BUHIMSCHI C. Uncultivated bacteria as etiologic agents in intra-amniotic inflammation leading to preterm birth. Journal of Clinical Microbiology, 2009, 47, 1, 38-47.
HERNANDEZ-RODRIGUEZ C., ROMERO-GONZALES R., ALBANI-CAMPANARIO M., FIGUEROA D., MERA-CRUZ N. & HERNANDEZ-GUERRERO C. Vaginal microbiota of healthy pregnant Mexican women is constitued by four Lactobacillus species and several vaginosis-associated bacteria. Infectious Diseases in Obstetrics and Gynecology, 2011, Article ID 851485 (9 pages). Doi: 10.1155/2011/851485.
HICKEY R.J., ZHOU X., PIERSON J.D., RAVEL J. & FORNEY L.J. Understanding vaginal microbiome complexity from an ecological perspective. Transl. Res., 2012, 160 (4), 267-282. Doi: 10.1016/j.trsl. 2012.02.008.
HUMMELEN R., MACKLAIN J.M., BISANZ J.E., HAMMOND J.O., McMILLAN A., VONGSA R., KOENIG D., GLOOR G.B. & REID G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLos ONE, 2011, 6,1, e26602
LAMONT R.F., SOBEL J.D., AKINS R.A., HASSAN S.S., CHAIWORAPONGSA T., KUSANOVIC J.P. & ROMERO R. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG, 2011, 118 (5), 533-549. Doi: 10 1111/j.1471-0528.2010.02840.x.
PAVLOVA S.I., KILIC A.O., KILIC S.S., SO J.S., NADER-MACIAS M.E., SIMOES J.A. & TAO L. Genetic diversity of vaginal lactobacilli from women in different countries based on 16S rRNA gene sequences. Journal of Applied Microbiology, 2002, 92, 451-459.
RAMPERSAUD R., RANDIS T.M. & RATNER A.J. Microbiota of the upper and lower genital tract. Semin Fetal Neonatal Med., 2012, 17 (1), 51-57.
SHAFER M.A., SWEET R.L., OHM-SMITH M.J., SHALWITZ J., BECK A. & SCHACHTER J. Microbiology of the lower tract genital tract in postmenarchal adolescent girls: differences by sexual activity, contraception, and presence of nonspecific vaginitis. J. Pediatr., 1985, 107 (6), 974-981.
SHIPITSYNA E., ROOS A., DATCU R., HALLEN A., FREDLUND H., JENSEN J.S., ENGSTRAND L. & UNEMO M. Composition of the vaginal microbiote in women of reproductive age-sensitive and specific molecular diagnosis of bacterial vaginosis is possible? PLos ONE, 2013, 8 (4): e60670. Doi: 10.1371/journal.pone.0060670.

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