New study links the cervicovaginal microbiome to an increased risk of chlamydia infections

New study links the cervicovaginal microbiome to an increased risk of chlamydia infections

Research shows how microbial imbalances increase susceptibility to infection and reinfection and provide potential avenues for prevention and treatment.

The cervicovaginal microbiome (CVM) plays a critical role in influencing the risk of genital tract infections. A recent study published incellinvestigates how the CVM affects the incidence and recurrence of Chlamydia trachomatis (CT) infections and associated complications.

Understanding Chlamydia trachomatis

CT is the most common bacterial sexually transmitted infection (STI), with over 130 million cases reported in 2019. Rising incidence over the past four decades has placed significant strain on public health systems.

A CT scan can lead to serious complications, including pelvic inflammatory disease (PID), miscarriage, chronic pelvic pain, infertility, and ectopic pregnancy. Infants born to mothers with CT are at risk of conjunctivitis and pneumonitis.

Adolescents and young adults (AYA) account for half of all new STI cases, with CT rates five times higher among Black and Hispanic AYAs compared to their white counterparts, highlighting stark disparities in health outcomes. Risk factors for CT include multiple sexual partners, previous sexually transmitted diseases, age under 25 years, low educational attainment, and vaginal dysbiosis, commonly referred to as bacterial vaginosis (BV). However, because BV and CT share similar risk factors, their relationship remains complex and disjointed.

The cervicovaginal microbiome

The CVM consists of bacteria and fungi that are typically dominated by lactobacilli or are characterized as polymicrobial. Important Lactobacillus species –L. crushatus, L. iners, L. gasseri and L. jensenii– produce lactic acid, creating an environment that inhibits CT colonization. Some species also reduce tryptophan levels, further limiting CT growth.

The CVM is categorized into molecular subtypes based on 16S rRNA gene sequencing and community state type (CST) clustering.

Study overview

The aim of the study was to examine the association between BV and CT over time while taking into account common risk factors. Researchers studied 560 black and Hispanic AYAs, including 187 women with newly diagnosed CT infections and 373 controls. The participants, aged 13 to 21 (average age 20), were all sexually active.

CVM samples were collected approximately six months before infection, during infection, and six months after infection. These samples were analyzed using a molecular BV score (molBV), an objective marker of CVM status similar to the Nugent score used to diagnose BV.

CT risk prediction

MolBV levels were significantly higher in individuals who later developed CT compared to controls. This difference was evident in samples before infection but disappeared after treatment, suggesting that CVM dysbiosis may increase susceptibility to CT.

Participants with BV-like CVM features, characterized by higher molBV values ​​and greater microbial diversity, showed a higher risk of CT. In particular, CST-IV-A, a subtype associated with Candidatus Lachnocurva vaginae, increased the risk of CT by 2.5-fold and was associated with recurrent infections.

Further stratification revealed that individuals with an mBV-positive CVM profile were 62% more likely to acquire CT. Those classified as mBV-A (associated with CST-IV-A) had a 2.4-fold higher risk compared to mBV-B.

Candidatus Lachnocurva vaginae – 33 times more common in mBV-A – can disrupt protective lactic acid production and weaken defense against CT. This species was closely associated with a network of ten bacterial genera, including Prevotella, Megasphaera and Clostridium, which together predicted a 2.5-fold increase in CT risk per unit increase in microbial risk score (MRS).

Wider impact on the CVM

CT infections resulted in significant changes in the CVM, although samples often returned to baseline composition after treatment. However, mBV-intermediate stages and CST-IV-A remained elevated in CT cases compared to controls.

mBV-A status not only predicted new infections, but also increased the risk of reinfection by 3.6-fold. Overall, reinfection rates were 20.6% in CT cases versus 4% in controls, representing a sixfold higher risk.

Furthermore, mBV-positive status after treatment correlated with increased miscarriage rates, highlighting the clinical importance of CVM composition.

Conclusions

The study concludes that CVM features associated with BV – such as mBV states, CSTs and specific bacterial taxa – strongly predict the risk of CT infection and reinfection. Loss of protective lactobacilli and increased microbial diversity provide biological support for these results.

These results highlight the importance of classifying BV by molecular subtype to better understand its relationship to CT. The role of the CVM in susceptibility, recurrence, and complications also highlights its potential as a target for preventive and therapeutic interventions.

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