Cervicovaginal microbiome and natural history of Chlamydia trachomatis in adolescents and young women Original paper

What was studied?

This original research article investigated the influence of the cervicovaginal microbiome (CVM) on the natural history of Chlamydia trachomatis (CT) infection in adolescents and young women. The study employed a longitudinal, nested case-control design to examine microbiome profiles before, during, and after incident CT infection. Using molecular methods, specifically 16S rRNA gene sequencing and the molBV algorithm, the researchers characterized the CVM and identified molecular subtypes of bacterial vaginosis (BV) and community state types (CSTs). The study further developed a microbial risk score (MRS) to evaluate the combined effect of key microbial genera associated with CT risk and explored the relationship between post-infection microbiome states, CT reinfection, and reproductive sequelae such as pelvic inflammatory disease (PID) and miscarriage.

Who was studied?

The study cohort comprised 560 sexually active adolescent and young adult women (ages 13–21) attending the Mount Sinai Adolescent Health Center in New York City. The participants were predominantly Black and Hispanic, populations known to have disproportionately higher rates of CT infection. A total of 187 women with incident CT were matched with 373 controls by age, enrollment year, and prior CT history. Cervicovaginal samples and behavioral data were collected approximately every six months, allowing for longitudinal assessment of microbiome composition and clinical outcomes. The study design ensured comparability of cases and controls with respect to sexual risk behaviors and demographic factors.

Most important findings

The study revealed that a molecular BV subtype defined by the presence of CST-IV-A (characterized by Candidatus Lachnocurva vaginae) was a significant and independent risk factor for incident CT infection. Elevated molBV scores and increased bacterial diversity were observed both before and during CT infection in cases compared to controls, supporting the role of CVM dysbiosis in CT susceptibility. Using a polymicrobial risk score, the researchers identified a network of 10 bacterial genera, including Candidatus Lachnocurva vaginae, Prevotella, and Megasphaera, whose collective presence strongly predicted CT acquisition. Following antibiotic treatment, the CVM of cases generally reverted to a baseline-like state; however, persistent or emergent mBV-A states (molBV-positive with CST-IV-A) were associated with a markedly increased risk of CT reinfection. Post-treatment mBV-positive states also trended toward higher rates of PID and miscarriage, although these associations were limited by sample size. Notably, sexual risk behavior was not a significant mediator of the microbiome-CT association in this homogenous, high-risk cohort.

Key implications

This study provides robust evidence that specific molecular subtypes of BV, particularly those characterized by CST-IV-A and Candidatus Lachnocurva vaginae, confer increased risk for both initial CT infection and reinfection, independent of traditional behavioral risk factors. The findings suggest that microbiome profiling, and particularly the identification of high-risk BV subtypes, could be leveraged for targeted interventions in populations at elevated risk for CT and its complications. These results highlight the potential for microbiome-based therapeutic and preventive strategies, such as probiotics or targeted antimicrobial approaches, to reduce the incidence of CT and its sequelae. Moreover, the data support the inclusion of detailed microbial community signatures, rather than single-species markers, in risk prediction models for sexually transmitted infections.