Vaginal Microbiome: Understanding Its Influence on Women's Sexual and Reproductive Health

The Vaginal Microbiome and Its Importance

Published by Synlab on 24 July 2024
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The vaginal microbiome is a topic of growing interest in medicine and scientific research due to its significance for women’s health. Understanding how the microbial community of the vagina influences immunity, nutrition, and overall well-being is crucial for doctors and specialists.

 

This article explores the composition, functions, and relevance of the vaginal microbiome, highlighting its implications for reproductive health and disease prevention. The human body hosts a rich diversity of microorganisms, forming a dynamic, functional, and supportive system that develops in harmony with the physiological progress of its host.

 

Thus, the microbiota plays a fundamental role in human physiological mechanisms, such as the development of immunity and nutrition, establishing a mutually beneficial relationship with the host, in which it provides shelter and nutrition. 

 

What is the Difference Between Microbiota and Microbiome? 

The term microbiota refers to the complex community of microorganisms that inhabit a specific location in the body, such as the gastrointestinal tract, skin, mouth, vagina, among others. 

 

The microbiota includes all bacteria, viruses, fungi, and other microorganisms that coexist in this environment, playing important roles in the health and functioning of the host organism. 

 

On the other hand, the term microbiome refers to the collective genome of a microbial consortium or community, meaning it is the complete set of genes of the microorganisms that form the microbiota (including the genetic material of all bacteria, viruses, fungi, and other microorganisms).  

Additionally, the term also refers to the activities and metabolic capabilities of the present microorganisms (1). 

 

The Importance of the Human Microbiome

In the early stages of life, the development of the microbiome influences immune function. Microorganisms acquired vertically, horizontally and through the environment, as well as their metabolic products, have the potential to shape developmental pathways that impact health throughout life (2). 

 

Thus, the microbiome plays a crucial role in the development of metabolic, immune and nutritional functions, necessitating careful attention. Understanding how complex microbial communities can affect the pathogenesis of various diseases has significant implications for their prevention, diagnosis, and treatment (3). 

 

In recent decades, the field of human microbiome research has evolved beyond merely cataloging the diversity of microorganisms, to understanding how these microorganisms constitute a dynamic and supportive functional system that develops synergistically, in parallel with the process of physiological development and decline (4-6). 

 

What is increasingly evident is that a wide range of conditions, including chronic inflammatory diseases (7), metabolic diseases (8), neurological disorders and cancer (9, 10), are now being linked to functional changes in the microbiome. 

 

These changes can occur both in isolation at the disease manifestation site and in mucosal areas or distant organ systems, triggering metabolic and immune changes in the host (1). 

 

Various factors, such as diet, antimicrobial agents and immunity, influence human microbiomes, especially the gut microbiome, which harbors the greatest quantity and variety of microorganisms. In response, bioactive products from the microbiome shape human cell function (11, 12). 

 

To better understand the influence of the gut microbiome on health, SYNLAB offers the MyBiome, a diagnostic test for the gut microbiome that performs a complete reading of the gut microbiome genome through massive sequencing (shotgun metagenomics). Read more about the intestinal microbiome and discover how MyBiome allows for an in-depth, objective, and actionable study of all the microorganisms that make up the intestinal ecosystem. 

 

The Vaginal Microbiome and Its Importance

 

Vaginal Microbiota and Microbiome 

The vaginal microbiota constitutes about 9% of the total human microbiota (13) and is considered a dynamic microenvironment where pregnancy, contraceptive use, menstrual cycle, and sexual activity contribute to variations in bacterial communities (14, 15). 

 

The normal vaginal flora is believed to be dominated by lactobacilli. The species L. iners, L. crispatus, L. gasseri, and L. jensenii have been shown to predominate the vaginal microbiota of healthy women of reproductive age in varying proportions (16-18). About 120 species of Lactobacillus have been documented, and 20 are known to inhabit the vagina. 

 

However, an altered vaginal microbiota with a low abundance of lactobacilli, especially during pregnancy, can result in excessive inflammation and risk of premature birth (19, 20). 

 

Furthermore, since the vaginal microbiome plays an important role in embryo implantation, it is not surprising that bacterial vaginosis is more common in infertile women and is associated with reduced conception rates (13). 

 

These microorganisms live in a mutualistic relationship with the vagina, protecting it from potentially pathogenic microorganisms such as those causing bacterial vaginosis, urinary tract infections, Candida infections, and sexually transmitted infections (STIs) (21). 

 

This contribution appears to be indispensable for reproductive success. The microbiota acts as a frontline defender against invading microorganisms through a phenomenon called “colonization resistance,” preventing foreign organisms from colonizing areas of the human body and causing infections (22). 

 

The concept of a global pattern of normality versus vaginal microbiome dysbiosis is subject to debate, as women of different ethnicities have distinct vaginal microbiotas with regional variations (23). 

 

However, despite the great variability among women, it is currently accepted that the “healthy state of the vaginal microbiome” in women of reproductive age is characterized by the dominant presence of one or, at most, two species of Lactobacillus, with L. crispatus, L. iners, L. gasseri, and L. jensenii being the most common. 

 

Through the production of lactic acid, lactobacilli can maintain an acidic environment in the vagina which, along with the production of other antimicrobial compounds, helps inhibit or control the growth of opportunistic and pathogenic microorganisms. 

 

What is Vaginal Dysbiosis?

The main constituents of the microbiome, bacteria, need to maintain constant symbiosis, which is the balance between commensal (beneficial) and pathogenic (harmful) bacteria. 

 

The opposite, known as dysbiosis, occurs when there is an imbalance in this relationship, triggering a pro-inflammatory microbiota pattern (3). Dysbiosis impairs health by increasing the host’s susceptibility to a spectrum of inflammatory and metabolic disorders (24). 

 

About 20-30% of women of reproductive age have an altered microbiome. Vaginal microbiota dysbiosis can be physiological or pathological, depending on the interaction of metabolic and microbial factors. The vaginal microbiota evolves with age, with anaerobic microorganisms being dominant in the prepubertal age, transitioning to a Lactobacillus-rich vagina in reproductive age (25). 

 

Imbalances in the vaginal microbiome are mainly caused by the depletion of Lactobacillus spp. Studies associate this decrease with an increased risk of sexually transmitted infections (STIs), as well as pregnancy complications (miscarriage and preterm birth) and less favorable in vitro fertilization outcomes (lower implantation rate and higher number of late miscarriages) (26, 27). 

 

Hormonal influence is also an important factor that determines the different phases of women’s reproductive cycles. Among the hormones, estrogens are known to induce specific modifications in the vaginal microbiota (28). 

 

Both physiological (pregnancy and menstrual cycle) and pathological (bacterial vaginosis, urinary tract infections, and sexually transmitted diseases) alterations are associated with significant changes in the vaginal microbiota (29). 

 

Therefore, in recent years, it has been recognized that the microbial community of the lower genital tract plays a fundamental role in maintaining women’s sexual and reproductive health. 

 

Vaginal Microbiome and Infertility 

The vaginal microbiome associated with bacterial vaginosis is believed to be a contributing factor to infertility in women of reproductive age (30). Women with idiopathic infertility show a higher incidence of abnormal vaginal microbiota (31). 

 

A systematic review study with meta-analysis on the association of bacterial vaginosis and infertility revealed that 19% of infertile women have bacterial vaginosis, while 39% had intermediate vaginal flora. 

 

Additionally, a higher prevalence of bacterial vaginosis was observed in infertile women compared to fertile women in the same age group, and this condition was related to reduced conception rates. 

 

These results reinforce the importance of the abundant presence of Lactobacillus species as a characteristic of healthy and normal vaginal flora (32). Therefore, a more comprehensive understanding of the functional elements, beyond the composition of the vaginal microbiome, can contribute to the improvement of diagnostic strategies and treatments. 

 

Which Test Does SYNLAB Offer for Investigating the Vaginal Microbiome? 

SYNLAB offers a metagenomic study of the vaginal microbiome, allowing for the analysis of the relative abundance of bacterial species that make up the vaginal microbial community through shotgun metagenomic sequencing (complete bacterial genome sequencing). 

 

This approach avoids the amplification bias inherent in conventional studies based on 16S rRNA analysis and provides more precise species-level information. 

 

Additionally, the test includes RT-PCR analysis for infections by Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium/hominis, Ureaplasma urealyticum/parvum, and the following seven Candida species: C. albicans, C. glabrata, C. parapsilosis, C. krusei, C. dubliniensis, C. tropicalis and C. lusitaniae. 

 

What Are the Advantages of the Metagenomic Study of the Vaginal Microbiome? 

The vaginal microbiome test offers a comprehensive view of the vaginal microbiome, allowing for: 

  • Characterization of the patient’s community state type (CST);
  • Objective establishment of different dysbiosis states by using cut-off points validated in clinical studies;
  • Precise characterization of the causal agents of infections, contributing to the optimization of the therapeutic approach for frequent vaginal tract infections;
  • A results report specifically designed to ensure quick and easy interpretation.

To illustrate how metagenomic analysis of the vaginal microbiome can assist in personalized treatments and more accurate diagnostics, we present a clinical case that exemplifies the benefits of this innovative approach in clinical practice. 

 

Clinical Case: 

A 35-year-old female patient, with a history of recurrent bacterial vaginosis, underwent a metagenomic analysis of her vaginal microbiome. The results revealed that nearly 97% of her vaginal microbiota was composed of bacteria not belonging to the Lactobacillus genus, indicating a case of vaginal dysbiosis. Among these, 44.6% consisted of Gardnerella vaginalis, a bacterium associated with CST IV (Community State Type IV), characterized by low production of lactic acid and bacteriocins, as well as elevated vaginal pH. 

 

This microbial imbalance promotes inflammation of the vaginal mucosa, a typical condition in bacterial vaginosis. Additionally, the predominance of Gardnerella vaginalis facilitates the proliferation of other anaerobic bacteria, such as Mobiluncus, which comprised 24.6% of the patient’s microbiota. Both species are known for forming biofilms, a type of shield that bacterial cells use around themselves as protection, making their elimination more difficult and the treatment more complex and challenging. 

 

Although the most commonly used antibiotics for bacterial vaginosis are metronidazole and clindamycin, this particular case required a different approach. The high abundance of Mobiluncus curtisii, a species linked to a higher risk of therapeutic failure and recurrence, was notable. This is because metagenomic analysis detected strains resistant to these antibiotics, which would not have been identified with traditional methods such as 16S sequencing. 

 

Thus, the ideal treatment for this patient involved the use of amoxicillin with clavulanate or an antibiotic from the macrolide class.  

 

However, due to the increased risk of opportunistic infections after treatment, such as candidiasis, and secondary side effects, such as diarrhea, it is advisable to complement the treatment with antiseptics, lactic acid, and probiotics, to restore the gut microbiota and acidify the vaginal environment. 

 

What Are the Indications for the Metagenomic Study of the Vaginal Microbiome? 

This study is especially indicated for women who: 

  • Have infertility issues (recurrent implantation failure, repeated miscarriages);
  • Patients suffering from recurrent vaginal infections (bacterial vaginosis, Candida spp, among others);
  • Patients with chronic pelvic pain;
  • Patients considering motherhood and/or wish to proactively assess their vaginal health.

 

What Is the Methodology of the Metagenomic Study of the Vaginal Microbiome?

The metagenomic study of the vaginal microbiome is performed through shotgun sequencing, which involves the random fragmentation of small DNA fragments that are then sequenced individually. 

 

Shotgun sequencing is an effective approach for sequencing entire genomes, especially for organisms whose genomes are too large to be sequenced traditionally. This method allows the complete study of the genomes of all bacteria and microorganisms that make up the vaginal ecosystem. 

 

This approach avoids the amplification bias inherent in conventional 16S ribosomal gene studies, which often focus on only a small portion (less than 20%) of the 16S rRNA gene (33). 

 

Shotgun sequencing provides comprehensive information about an organism’s genome, enabling the analysis of genes, metabolic pathways, and regulatory elements, since the entire genome, including millions to billions of base pairs, is sequenced. 

 

In contrast, 16S gene sequencing is employed only to identify and classify bacteria present in a sample, it sequences only a specific region of the 16S rRNA gene, which is relatively short (about 1,500 bases) (33). 

 

Get to Know the SYNLAB Group, a Reference in Medical Diagnostic Services!

Performing precise and up-to-date tests is essential for making more accurate diagnoses and better directing treatments. SYNLAB is here to help you. 

 

We offer diagnostic solutions with rigorous quality control to the companies, patients, and doctors we serve. We have been operating in Brazil for over 10 years, working in 36 countries and three continents, and we are leaders in service provision in Europe. 

 

Contact the SYNLAB team and learn about the available tests. 

 

References 

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(2) Rackaityte E, Lynch SV. The human microbiome in the 21st century. Nat Commun. 2020 Oct 16;11(1):5256. doi: 10.1038/s41467-020-18983-8.

 

(3) Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defning the human microbiome. Nutr Ver. 2012;70(Suppl 1):S38-44.

 

(4) Hollister, E. B. et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome. 2015;3,36.

 

(5) Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488,178–184.

 

(6) Stewart, C. J. et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562,583–588.

 

(7) Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front. Immunol. 2014;5,427.

 

(8) Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500,541–546.

 

(9) Cryan, J. F., O’Riordan, K. J., Sandhu, K., Peterson, V. & Dinan, T. G. The gut microbiome in neurological disorders. Lancet Neurol. 2020;19,179–194.

 

(10) Nejman, D. et al. The human tumor microbiome is composed of tumor type specific intracellular bacteria. Science. 2020;368,973–980.

 

(11) Hepworth, M. R. et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature. 2013;498, 113–117.

 

(12) Scharschmidt, T. C. et al. A wave of regulatory T Cells into neonatal skin mediates tolerance to commensal microbes. Immunity. 2015;43,1011–1021.

 

(13) Sirota I, Zarek SM, Segars JH. Potential infuence of the microbiome on infertility and assisted reproductive technology. Semin Reprod Med. 2014;32(1):35–42.

 

(14) Gajer P, Brotman RM, Bai G, Sakamoto J, Schütte UM, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 2012 https://doi.org/10.1126/scitranslmed.3003605

 

(15) Huang Y, Merkatz RB, Hillier SL, Roberts K, Blithe DL, et al. Efects of a one year reusable contraceptive vaginal ring on vaginal microfora and the risk of vaginal infection: an open-label prospective evaluation. PLoS ONE . 2015;10(8):e0134460.

 

(16) Martínez-Peña MD, Castro-Escarpulli G, Aguilera-Arreola MG. Lactobacillus species isolated from vaginal secretions of healthy and bacterial vaginosis-intermediate Mexican women: a prospective study. BMC Infect Dis. 2013;13:189.

 

(17) Pendharkar S, Magopane T, Larsson PG, de Bruyn G, Gray GE, et al. Identifcation and characterisation of vaginal lactobacilli from South African women. BMC Infect Dis. 2013;13:43.

 

(18) Drell T, Lillsaar T, Tummeleht L, Simm J, Aaspõllu A, Väin E et al. Characterization of the vaginal micro-and mycobiome in asymptomatic reproductive-age Estonian women. PLoS ONE. 2013;8(1):e54379.

 

(19) Hyman RW, Fukushima M, Jiang H, Fung E, Rand L, Johnson B et al. Diversity of the vaginal microbiome correlates with preterm birth. Reprod Sci. 2014;21(1):32–40.

 

(20) Aagaard K, Riehle K, Ma J, Segata N, Mistretta TA, Coarfa C, et al. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS ONE. 2012;7(6):e36466

 

(21) Sobel JD. Is There a protective role for vaginal fora? Curr Infect Dis Rep. 1999;1(4):379–383.

 

(22) Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–1638.

 

(23) Saraf VS, Sheikh SA, Ahmad A, et al. Vaginal microbiome: normalcy vs dysbiosis. Arch Microbiol. 2021;Sep;203(7):3793-3802.

 

(24) Panda S, Guarner F, Manichanh C. Structure and functions of the gut microbiome. Endocr Metab Immune Disord Drug Targets. 2014;14(4):290–299.

 

(25) Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011;108(Suppl 1):4680–4687.

 

(26) Skafte-Holm A, Humaidan P, Bernabeu A, Lledo B, Jensen JS, Haahr T. The Association between Vaginal Dysbiosis and Reproductive Outcomes in Sub-Fertile Women Undergoing IVF-Treatment: A Systematic PRISMA Review and Meta-Analysis. Pathogens. 2021;10(3):295.

 

(27) Gudnadottir U, Debelius JW, Du J, Hugerth LW, Danielsson H, et al. The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis. Sci Rep. 2022;12(1):7926.

 

(28) Farage MA, Miller KW, Sobel JD (2010) Dynamics of the vaginal ecosystem—hormonal Infuences. Infect Dis: Res Treat. https://doi.org/10.4137/IDRT.S3903

 

(29) Lamont RF, Sobel JD, Akins RA, Hassan SS, Chaiworapongsa T, et al. The vaginal microbiome: new information about genital tract fora using molecular based techniques. BJOG. 2011;118(5):533–549.

 

(30) Mania-Pramanik J, Kerkar SC, Salvi VS. Bacterial vaginosis: a cause of infertility? Int J STD AIDS. 2009;20(11):778–781.

 

(31) Spandorfer SD, Neuer A, Giraldo PC, Rosenwaks Z, Witkin SS. Relationship of abnormal vaginal fora, proinfammatory cytokines and idiopathic infertility in women undergoing IVF. J Reprod Med. 2001;46(9):806–810.

 

(32) van Oostrum N, De Sutter P, Meys J, Verstraelen H. Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 2013;28(7):1809–1815.

 

(33) Ranjan R, Rani A, Metwally A, McGee HS, Perkins DL. Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing. Biochem Biophys Res Commun. 2016;22;469(4):967-77.

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