The Role of L. iners in Vaginal Health: Insights and Controversies

Vaginal microbes play a crucial role in maintaining genital health by offering powerful defenses against infections. Unlike healthy microbiota in other parts of the body, such as the gastrointestinal tract, the vaginal microbiota is distinctive for its low diversity with lactobacilli comprising nearly 95% of the total bacteria. Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, and Lactobacillus iners, are the most represented in the vagina of healthy women

However, L. iners is distinct from the others because of its variable connections with genital health. This blog will describe the unique characteristics of L. iners as they pertain to vaginal health as well as the controversies surrounding their actions. Ideas on how this knowledge may influence modulation therapy will be discussed.

L. iners in the vaginal microbiome, in brief

As a fundamental contributor to genital and reproductive health, the vaginal microbiome defends against bacterial vaginosis and sexually transmitted infections. Lactobacilli species, including L. crispatus, L. gasseri, L. jensenii, and L. iners protect against many pathogens in diverse ways. These include competing against pathogens for nutrients, producing lactic acid which acidifies the environment and kills pathogens, producing bacteriocins that also suppress harmful bacteria, creating a physical barrier against pathogen adhesion, and exerting immune modulatory effects.

Various factors like menstruation, pregnancy, sexual practices, vaginal douching, and antibiotics can swiftly disturb the vaginal ecosystem, potentially causing or facilitating conditions including bacterial vaginosis (BV), sexually transmitted infections (STIs), and pregnancy-related complications.

First identified in 1999, L. iners is the most common and persistent vaginal species in reproductive-aged women across the world. Under fluctuating conditions such as high pH or dysbiosis — when other species may die — L. iners survives with remarkable consistency and adaptability. Unlike the other primary vaginal lactobacilli species like L. crispatus, L. jensenii, and L. gasseri, it is implicated in both healthy and disease states.

L. iners and disease

In bacterial vaginosis (BV), pathogens interrupt the healthy vaginal habitat, potentially elevating the risk for sexually transmitted diseases and leading to adverse outcomes regarding reproductive health.

Researchers have found that levels of protection vary by type of dominant species. Whereas the presence of L. crispatus is linked with good health in numerous studies, dominance by L. iners is not always reported to offer protection against vaginal dysbiosis. Vaginal microbiota primarily dominated by L. iners have been linked to a higher likelihood of experiencing bacterial vaginosis.

A 2023  systematic review and meta-analyses looked at the associations between L. iners compared with L. crispatus in outcomes in BV and Chlamydia trachomatis (CT) – as well as in other sexually-transmitted infections.

Bacterial vaginosis

In the three BV studies included in the meta-analysis, L.iners–dominated microbiota had two times the prevalence of BV compared with microbiota dominated by L. crispatus.

Chlamydia trachomatis 

In the six CT studies included in the meta-analysis, L.iners–dominated microbiota were observed to have a 3.4-fold higher probability of CT compared with microbiota dominated by L. crispatus.

The researchers were unable to make conclusions regarding links between L. iners and the other outcomes (human papillomavirus, cervical dysplasia, human immunodeficiency virus, genital herpes, Trichomonas vaginalis, and Neisseria gonorrhoeae) because “evidence was too sparse to perform meta-analysis.”  The authors cautioned that a high risk of bias and low-quality evidence in these studies makes interpretation regarding the impact of L. iners on sexual health outcomes difficult.

The link between L. iners and an elevated risk of negative outcomes is not consistent, leading to widespread debate regarding its role in the vaginal microbiome.

Possible mechanisms

Recent research points to several unique characteristics of L. iners, which may at least partially account for some of its inconsistent role in vaginal health and disease.

Lactic acid production

Lactic acid exists as two isomers and both acidify (lower the pH) the vaginal milieu, a key protection against pathogens. L-lactic acid is derived from both the vaginal epithelia and Lactobacillus spp., while D-lactic acid is produced by specific lactobacilli. While there are observed differences in lactic acid production by diverse lactobacilli, including L. iners, the significance is not clear.

Strain

Of the vaginal Lactobacillus spp., L. iners has the smallest genetic blueprint but its different strains show more genetic diversity. The specific combination of L. iners strains in the vaginal microbiome has a broad range of functions that help the species thrive in different vaginal environments. However, current studies often group together strain-specific effects, leading to less accurate assessments of the risks associated with this bacterial species.

Gene expression

L. liners gene activity in the vaginal microbiome shows its adaptability to environmental changes. The ability of L. iners to produce a protein toxin named inerolysin influences its ability to acquire nutrients from the vaginal environment and may give L. iners a competitive advantage when nutrients are scarce, especially under potentially adverse conditions, such as BV, when other lactobacilli species struggle to colonize the vagina. Furthermore, new research suggests that additional bacteriocin production as well as selective sensitivity to bacteriocins may factor into the adaptation of L.iners in hostile vaginal conditions.  

Going forward

Though somewhat admirable, the persistence and plasticity of L. iners in the vaginal environment make for a challenging quandary when it comes to disease protection. Other lactobacilli-containing therapies have shown some encouraging results in conditions such as BV, CT, and other disorders such as human immunodeficiency virus ( HIV), human papillomavirus (HPV) as well as in obstetric and reproductive disorders.

Certain strains or genes of L. iners could potentially serve as targets for therapeutic adjustments to the vaginal microbiota.  An innovative approach might involve stabilizing the L. iners microbiota, particularly those linked to a higher risk of BV, by transitioning them to a more resilient state characterized by L. iners strains resistant to fluctuations.

Takeaway

Vaginal microbes, particularly lactobacilli, play a vital role in safeguarding genital health by defending against infections. While L. crispatus, L. gasseri, and L. jensenii are associated with positive outcomes, L. iners, one of the most common vaginal species, shows unique adaptability under fluctuating conditions but has controversial connections with health. Studies indicate L.iners–dominated microbiota may elevate the risk of bacterial vaginosis and Chlamydia trachomatis and possibly other outcomes. The many questions regarding L. iners make for challenging issues in understanding its role in the vaginal microbiome. Innovative therapeutic approaches targeting specific L. iners strains or genes could potentially modulate the vaginal microbiota and address associated health risks.

Image by Gerd Altmann from Pixabay

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