The cervicovaginal microbiome (CVM) plays a significant role in shaping the risk of genital tract infections. A recent study published in Cell has unveiled important findings on how the CVM influences the incidence, recurrence, and complications of Chlamydia trachomatis (CT) infections, the most common bacterial sexually transmitted infection (STI) worldwide.
Understanding Chlamydia trachomatis (CT)
Chlamydia trachomatis, often simply referred to as CT, is the most prevalent STI, with over 130 million cases reported globally in 2019. Its rising incidence over the past few decades has placed significant strain on public health systems, particularly as CT infections can lead to severe complications, such as pelvic inflammatory disease (PID), chronic pelvic pain, infertility, miscarriage, and ectopic pregnancy. Infants born to mothers with CT infections are also at risk of developing conjunctivitis and pneumonitis.
Adolescents and young adults (AYA) account for nearly half of all new STI cases, with CT rates being disproportionately higher among Black and Hispanic AYAs. Risk factors for CT include multiple sexual partners, prior STIs, age under 25, low educational attainment, and vaginal dysbiosis—commonly known as bacterial vaginosis (BV). Although BV and CT share many common risk factors, their relationship remains complex and not yet fully understood.
The Cervicovaginal Microbiome (CVM)
The CVM is composed of a variety of microorganisms, including bacteria and fungi, that typically exist in a balanced state. A healthy CVM is dominated by lactobacilli, such as L. crispatus, L. iners, L. gasseri, and L. jensenii, which produce lactic acid to maintain an acidic environment that inhibits the growth of pathogens like CT. Some lactobacillus species also reduce tryptophan levels, further hindering CT growth. However, in cases of CVM dysbiosis, which is often associated with BV, this protective balance is disrupted, and harmful bacteria are allowed to thrive, potentially increasing the risk of CT infection.
The CVM can be classified into various molecular subtypes using 16S rRNA gene sequencing and community state type (CST) clustering. This classification helps to better understand the diversity and health of the microbiome and its potential role in disease susceptibility.
Study Overview
The study sought to examine the relationship between BV and CT over time while controlling for shared risk factors. Researchers analyzed 560 Black and Hispanic adolescents and young adults, including 187 women diagnosed with newly acquired CT infections and 373 controls. Participants were aged 13 to 21 years, with a mean age of 20, and were all sexually active.
CVM samples were collected at three different time points: approximately six months before infection, during the infection, and six months after infection. Researchers used a molecular BV score (molBV), an objective marker of CVM health, to assess the microbiome’s status, much like the Nugent score is used to diagnose BV.
Predicting Chlamydia Risk
The results of the study indicated that individuals who later developed CT infections had significantly higher molBV scores prior to infection compared to the control group. This difference was evident in pre-infection samples but disappeared after treatment, suggesting that CVM dysbiosis—specifically an imbalanced microbiome—may increase the susceptibility to CT infections.
Particularly, participants with BV-like CVM features, characterized by higher molBV scores and greater microbial diversity, were at a significantly higher risk of contracting CT. One specific community state type (CST-IV-A), associated with Candidatus Lachnocurva vaginae, was found to increase the risk of CT infection by 2.5 times and was linked to recurrent infections.
Further analysis revealed that individuals with an mBV-positive CVM profile were 62% more likely to acquire CT compared to those with an mBV-negative profile. Specifically, those classified as mBV-A, associated with CST-IV-A, were found to have a 2.4-fold higher risk of CT infection compared to the mBV-B profile.
Interestingly, Candidatus Lachnocurva vaginae, which was 33 times more prevalent in the mBV-A profile, is believed to disrupt the production of protective lactic acid, weakening the natural defense against CT. This bacterium was also closely linked to a network of other bacterial genera, such as Prevotella, Megasphaera, and Clostridium, which collectively predicted a 2.5-fold increase in CT risk for every unit rise in microbial risk score (MRS).
Broader Impacts on the CVM
The study also revealed that CT infections caused significant changes to the CVM composition. While post-treatment samples typically returned to baseline, mBV-intermediate states and CST-IV-A remained elevated in those with CT infections compared to controls. Notably, the mBV-A state was not only associated with the initial risk of acquiring CT but also with a 3.6-fold increased risk of reinfection.
Overall, reinfection rates were substantially higher in CT cases (20.6%) compared to controls (4%), indicating a sixfold higher risk of reinfection for those with a dysbiotic microbiome. Additionally, mBV-positive CVM profiles post-treatment were associated with an increased risk of miscarriage, highlighting the broader clinical significance of CVM composition.
Conclusions
This study underscores the strong predictive relationship between CVM features—particularly BV-associated molecular subtypes like mBV states and CSTs—and the risk of CT infection and reinfection. The loss of protective lactobacilli and increased microbial diversity create a favorable environment for CT colonization and persistence. These findings highlight the importance of classifying BV by molecular subtype to better understand its role in CT susceptibility.
The study also demonstrates the potential of the CVM as a target for preventive and therapeutic interventions. By modulating the composition of the CVM, it may be possible to reduce the risk of CT infections and their recurrence, offering a new avenue for addressing the global burden of this common STI.
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