Evaluation of the Vaginal Microbiome in Clinical Diagnosis and Management of Vaginal Infectious Diseases

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Evaluation of the Vaginal Microbiome in Clinical Diagnosis and Management of Vaginal Infectious Diseases

The vaginal microbiome is a complex and dynamic ecosystem that plays a crucial role in maintaining vaginal health. Imbalances in this microbiome can lead to various vaginal infections, such as vulvovaginal candidiasis (VVC), bacterial vaginosis (BV), and aerobic vaginitis (AV). Understanding the vaginal microbiome and its changes is essential for the accurate diagnosis and effective management of these infections. This article explores the significance of the vaginal microbiome in clinical practice, the development of the Vaginal Microecology Evaluation System (VMES), and its application in diagnosing and managing vaginal infectious diseases.

Introduction to the Vaginal Microbiome

The human microbiome, often referred to as the “second human genome,” is a collection of microorganisms that reside in and on the human body. The urogenital tract contributes approximately 9% of the entire human microbiome, with the gastrointestinal tract accounting for 29%. The vaginal microbiome is particularly intricate, consisting of diverse microbial communities that can rapidly change in response to various factors, including age, pregnancy, menstruation, and antibiotic use. These changes can lead to dysbiosis, which is associated with infections such as VVC, BV, and AV.

The vaginal microbiome is dominated by Lactobacillus species in healthy women. These bacteria play a protective role by producing lactic acid, hydrogen peroxide (H2O2), and bacteriocins, which create an acidic environment (pH 3.8–4.4) that inhibits the growth of pathogenic microorganisms. Lactobacilli also prevent the adherence of pathogens to vaginal epithelial cells through competitive exclusion and bacterial interference. However, when the balance of the vaginal microbiome is disrupted, it can lead to infections that require clinical intervention.

The Vaginal Microecology Evaluation System (VMES)

To better understand and manage the vaginal microbiome, the Vaginal Microecology Evaluation System (VMES) was developed. This system provides a comprehensive assessment of the vaginal microbiome by evaluating both morphological and functional indicators. The VMES is a valuable tool for clinicians in diagnosing and managing vaginal infections, as it offers insights into the microbial composition and functional status of the vaginal ecosystem.

Morphological Indicators

Morphological indicators assessed by the VMES include bacterial density, flora diversity, dominant bacterial flora, inflammation markers (such as white blood cell count), and the presence of pathogenic microorganisms. The system also incorporates the Nugent score for BV and the AV score for AV, which provide additional diagnostic information.

  • Bacterial Density: This refers to the intensity of bacterial distribution in the vaginal flora, reflecting the total biomass. Normal bacterial density is classified as degree II (10–100 bacteria per field), while degree III (100–1000 bacteria per field) is also considered normal. Degrees I (1–10 bacteria per field) and IV (>1000 bacteria per field) indicate abnormal density.

  • Flora Diversity: This measures the variety of bacterial species present in the vaginal flora. Normal diversity is classified as degree II (4–6 types per field) or degree III (7–9 types per field). Degrees I (1–3 types per field) and IV (>10 types per field) indicate abnormal diversity.

  • Dominant Bacterial Flora: In healthy women, the dominant flora consists of large Gram-positive rods (Lactobacillus species). The presence of Gram-positive cocci (e.g., Staphylococcus aureus), Gram-negative rods (e.g., Escherichia coli), or other morphotypes may indicate an abnormal state.

  • Nugent Score: This score is used to diagnose BV and ranges from 0 to 10. A score of 0–3 is considered BV-negative, 4–6 is intermediate, and 7–10 is BV-positive.

  • AV Score: This score is used to diagnose AV. A score of less than 3 is considered normal, while a score of 3 or higher indicates AV.

Functional Indicators

Functional indicators assess the metabolic activity and functional status of the vaginal microbiome. These include vaginal pH, H2O2 production, and the activity of specific enzymes such as sialidase, β-glucuronidase, leukocyte esterase, and acetylglucosaminidase.

  • Vaginal pH: The normal vaginal pH ranges from 3.8 to 4.5. A pH below 3.8 or above 4.5 may indicate an imbalance in the vaginal microbiome.

  • H2O2 Production: H2O2 is primarily produced by Lactobacillus species. The presence of H2O2 is a positive functional indicator, as it reflects the activity of lactobacilli.

  • Enzyme Activity: The activity of enzymes such as sialidase (a marker of BV), β-glucuronidase (a marker of AV), leukocyte esterase (an indicator of inflammation), and acetylglucosaminidase can provide additional diagnostic information.

Vaginal Cleanliness

Vaginal cleanliness is another important indicator assessed by the VMES. It is used to judge the inflammation status of the vagina. Degrees II to III represent a normal vaginal microecological status, while degrees III to IV indicate an abnormal status, often associated with vaginal infections.

Recognizing the Vaginal Microbiome in Healthy Women

Understanding the normal vaginal microbiome is essential for identifying deviations that may lead to infections. In healthy women, the vaginal microbiome is dominated by Lactobacillus species, which maintain a low pH and produce antimicrobial compounds. The Human Microbiome Project has demonstrated that the vaginal microbiome of healthy women contains 10^8 to 10^9 colony-forming units per gram (CFU/g) of bacteria, with Lactobacillus species constituting 10^7 to 10^8 CFU/g of vaginal fluid.

More than 20 species of lactobacilli have been detected in the vagina, with the most common being Lactobacillus crispatus, Lactobacillus iners, Lactobacillus jensenii, and Lactobacillus gasseri. These species are responsible for metabolizing glycogen from vaginal epithelial cells into glucose and lactic acid, which helps maintain an acidic environment that inhibits the growth of pathogens.

Management of Vulvovaginal Candidiasis (VVC)

VVC is the second most common vaginal infection after BV. It is characterized by symptoms such as abnormal leucorrhea, itching, and irritation. The VMES is used to diagnose VVC by microscopically examining vaginal swab samples for the presence of spores, hyphae, and blastospores.

The first-line treatment for VVC includes azoles or polyene drugs. However, the use of probiotics, particularly Lactobacillus species, has shown clinical benefits in improving cure rates and preventing recurrences. Probiotics help restore the balance of the vaginal microbiota, promote the repopulation of lactobacilli, and re-establish normal vaginal pH. Lactobacilli exert their protective role through the production of antimicrobial compounds, competitive exclusion of pathogens, and immunomodulation.

Management of Bacterial Vaginosis (BV)

BV is characterized by a milky, homogeneous, malodorous vaginal discharge and is caused by a disruption in the vaginal microbiota. The VMES is used to diagnose BV by combining the Nugent score with the presence of clue cells in vaginal swab samples. Sialidase, produced by anaerobic Gram-negative bacterial rods, is a specific marker of BV.

The standard treatment for BV includes topical clindamycin cream, metronidazole gel, or oral metronidazole. Combining metronidazole with lactobacilli has been shown to be more effective than metronidazole alone. Vaginal administration of probiotic Lactobacillus species helps restore the normal vaginal microbiota and reduces the risk of BV recurrence. Normalizing vaginal pH using intravaginal boric acid has also been demonstrated to be effective in treating BV.

Management of Aerobic Vaginitis (AV)

AV, also known as desquamative inflammatory vaginitis, is characterized by purulent vaginal discharge and a strong inflammatory reaction. The VMES is used to diagnose AV based on the AV score. β-glucuronidase, produced by Escherichia coli and Group B streptococcus, is a specific marker of AV. Coagulase activity, associated with infections by Staphylococcus aureus, Enterococcus faecalis, and E. coli, is another marker of AV.

Treatment guidelines for AV are still limited, but non-antibiotic therapies, such as vaginal or oral probiotics, have been proposed. Women with AV characterized by a heavy parabasal-cell component may benefit from intravaginal estrogen therapy, which helps restore the vaginal mucosa.

Conclusion

The Vaginal Microecology Evaluation System (VMES) is a valuable tool in the clinical diagnosis and management of vaginal infections. By providing a comprehensive assessment of the vaginal microbiome, the VMES helps clinicians make prompt and accurate diagnoses and develop effective treatment regimens. The ultimate goal of managing vaginal infections is to restore the normal vaginal microecology, thereby improving patient outcomes and preventing recurrences.

doi.org/10.1097/CM9.0000000000000211

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