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

What was studied?

The focus keyphrase cervicovaginal microbiome and Chlamydia trachomatis anchors this investigation into how cervicovaginal microbial patterns influence the natural history of Chlamydia trachomatis infection in adolescents and young women. This longitudinal, nested case-control study examined cervicovaginal samples collected before, during, and after incident CT infection to determine how bacterial community structure, molecular bacterial vaginosis (mBV) states, and community state types (CSTs) shape susceptibility, reinfection, and downstream clinical outcomes such as pelvic inflammatory disease and miscarriage. The study leveraged 16S rRNA sequencing, ITS1 profiling, and a validated molBV algorithm to characterize microbial configurations associated with CT risk.

Who was studied?

Researchers followed 560 sexually active Black and Hispanic adolescent and young adult females receiving care at the Mount Sinai Adolescent Health Center. Cases (n=187) had incident CT infection, matched to 373 controls by age, enrollment year, prior CT history, and follow-up time. Samples were taken at three key points: approximately six months before infection (t−1), at infection diagnosis (t0), and six months after treatment (t+1). This population—at disproportionately high risk for CT—provided a crucial context for understanding structural microbial contributors distinct from sexual behavior, which showed limited variability across participants.

Most important findings

The study uncovered a powerful microbial signature predicting CT acquisition. Elevated molBV scores—particularly the mBV-positive category—were strongly associated with prospective CT risk, and deeper stratification revealed that CST-IV-A combined with mBV-positive (mBV-A) was the dominant risk-bearing subtype. This CST is characterized by Candidatus Lachnocurva vaginae, which showed a 33-fold higher abundance in mBV-A and demonstrated exceptional predictive performance (AUC 0.93). A validated microbial risk score (MRS) identified a coherent network of ten highly correlated bacterial genera—including Lachnocurva, Prevotella, Megasphaera, Clostridium, and others—whose combined effect far exceeded risk from any single taxon. The transition analysis revealed that cases were more likely than controls to shift toward mBV-positive states between t−1 and t0, suggesting a dynamic predisposition toward dysbiosis preceding infection. At t0, CT infection coincided with higher bacterial diversity, elevated CST-IV-A and CST-IV-B frequencies, and 37 differentially abundant species. Although post-treatment microbial communities appeared broadly resilient, cases still showed elevated mBV-intermediate and CST-IV-A levels at t+1, and the same mBV-A subtype predicted reinfection, with an adjusted rate ratio of 3.58.

Key implications

This study clarifies that CT risk is not merely behavioral—it is strongly shaped by cervicovaginal microbial ecology. A precise BV subtype (mBV-A) and its associated microbial network constitute a biologically plausible risk architecture involving loss of lactobacilli, excess anaerobes, and potential disruption of D-lactic acid–mediated protection. Clinically, these findings support incorporating microbial profiling into STI risk assessment, reinfection prevention strategies, and targeted microbiome-modulating therapies.

Citation

Usyk M, Carlson L, Schlecht NF, et al. Cervicovaginal microbiome and natural history of Chlamydia trachomatis in adolescents and young women. Cell. 2025;188:1051-1061. doi:10.1016/j.cell.2024.12.011. PIIS0092867424014247