The Endometrial Microbiome

Version For Professionals

The endometrial microbiome, a relatively recent focus in reproductive medicine, significantly impacts fertility and pregnancy outcomes. This microbiome comprises the bacterial communities residing in the endometrial cavity and the endometrium itself, which can influence endometrial receptivity, implantation success, and overall reproductive health.

Composition of the Endometrial Microbiome

The endometrial microbiome is a low-biomass microbiota, meaning it contains fewer bacterial cells compared to other body sites like the gut. Despite its lower bacterial load, the endometrial microbiome is diverse and plays a significant role in reproductive health. It includes a variety of bacterial species, with Lactobacillus being predominant in a healthy endometrium. However, the presence and balance of other bacterial genera also play crucial roles.

  • Dominant Species:

Lactobacillus: The most abundant and health-associated bacteria in the endometrium are typically from the Lactobacillus genus. These bacteria are essential for maintaining a protective environment against pathogens and supporting reproductive processes. Lactobacilli produce lactic acid, which helps maintain an acidic pH, creating a hostile environment for pathogenic bacteria. They also secrete hydrogen peroxide and bacteriocins, which further inhibit the growth of harmful microbes. High levels of Lactobacillus are associated with better reproductive outcomes, including higher implantation rates and successful pregnancies.

  • Pathogenic Species:

Gardnerella: This bacterium is often associated with bacterial vaginosis and can cause significant disruption to the vaginal and endometrial microbiomes. Its presence in the endometrium is linked to inflammation and adverse reproductive outcomes.

Atopobium: Similar to Gardnerella, Atopobium is another bacterium commonly found in cases of bacterial vaginosis. It contributes to the imbalance and can negatively impact the endometrial environment, potentially leading to issues with implantation and pregnancy maintenance.

Streptococcus: While Streptococcus species are part of the normal flora in many parts of the body, certain strains can be pathogenic in the endometrial environment. They are associated with infections and can disrupt the delicate balance of the microbiome, leading to dysbiosis.

Other Genera: In addition to the above, other bacterial genera such as Escherichia, Staphylococcus, and Bacteroides can also be present. While some of these bacteria may be harmless or even beneficial in other parts of the body, their overgrowth in the endometrium can be detrimental. They can contribute to chronic inflammation, which is harmful to reproductive health and can impede embryo implantation and development.

Mechanisms of Impact

  • Immune Modulation: The balance between beneficial and harmful bacteria in the endometrial microbiome influences the local immune environment. Lactobacilli promote anti-inflammatory responses and support the immune tolerance necessary for successful implantation. In contrast, pathogenic bacteria can trigger inflammatory pathways, leading to a hostile environment for an embryo.
  • Barrier Integrity: A healthy endometrial microbiome helps maintain the integrity of the endometrial lining. Beneficial bacteria support the expression of tight junction proteins, which keep the cells of the endometrial lining tightly joined. Pathogenic bacteria can disrupt this barrier, increasing the risk of infections and reducing the endometrium’s ability to support embryo implantation.
  • Metabolic Interactions: Microbial metabolites, such as short-chain fatty acids (SCFAs) produced by beneficial bacteria, play roles in cellular processes that affect implantation. SCFAs influence cell proliferation, differentiation, and apoptosis in endometrial cells, thereby modulating endometrial receptivity. An imbalance in the microbiome can alter these metabolic processes, negatively impacting reproductive outcomes.

Impact on Reproductive Health

The composition of the endometrial microbiome is closely linked to reproductive success. Several studies have shown that a Lactobacillus-dominated microbiota correlates with higher implantation rates, successful pregnancies, and live births. In contrast, a microbiota dominated by non-Lactobacillus species is associated with lower implantation rates, higher miscarriage rates, and overall poor reproductive outcomes​​​​.

  • Positive Outcomes: A high abundance of Lactobacillus species in the endometrium is linked to increased implantation and pregnancy success rates. These bacteria produce lactic acid, which maintains a low pH environment, inhibiting the growth of harmful bacteria​​.
  • Negative Outcomes: The presence of pathogenic bacteria such as Gardnerella and Atopobium can lead to inflammation and an unfavourable environment for embryo implantation. These bacteria are often associated with bacterial vaginosis and other reproductive tract infections, which can extend to the endometrium and disrupt its normal function​​​​.

Investigations

  1. 16S rRNA Gene Sequencing: This technique identifies bacterial populations based on their genetic material. It is widely used to analyse the composition of the endometrial microbiome and detect microbial dysbiosis.
  2. Culturomics: This high-throughput culture method isolates and identifies viable bacteria that might not be detected through sequencing alone. It provides a comprehensive view of the microbiome by cultivating a broader range of bacterial species​​.
  3. Next-Generation Sequencing (NGS): NGS technologies enable detailed analysis of the microbiome by sequencing large numbers of DNA molecules simultaneously. This method provides insights into the diversity and abundance of bacterial species present in the endometrium​​.
  4. EMMA and ALICE Tests: EMMA (Endometrial Microbiome Metagenomic Analysis) provides a complete view of the endometrial microbiome composition and recommends treatments to restore an optimal microbiome. ALICE (Analysis of Infectious Chronic Endometritis) detects bacteria causing chronic endometritis and suggests appropriate antibiotics​​.

Treatments

  1. Probiotics: Administering probiotics, particularly Lactobacillus species, aims to restore a healthy microbiome balance in the endometrium. This approach has shown promise in improving implantation rates and pregnancy outcomes in women undergoing ART​​.
  2. Antibiotic Therapy: Targeted antibiotics can treat infections caused by pathogenic bacteria identified through diagnostic tests like ALICE. This treatment is crucial for resolving chronic endometritis and other microbial imbalances that impair reproductive success​​​​.

Personalized Medicine: Based on diagnostic results, personalized treatment plans can be developed to address specific microbial imbalances. This approach may include a combination of antibiotics and probiotics to optimize the endometrial environment for implantation and pregnancy​​​​.