Variations in the Cervicovaginal Microbiota and Metabolite Profiles of Pregnant Women with and without Short Cervix

Spontaneous preterm birth (sPTB) is significantly associated with neonatal morbidity and mortality, with a short cervix (cervical length (CL) ≤25 mm) being a key predictor; its underlying molecular mechanisms remain unclear. This prospective case‒control study enrolled 36 singleton pregnancies between 16–20 weeks of gestation categorized into short cervix (n = 18) and control (n = 18) groups. Microbial and metabolic profiles were analyzed using 16S rRNA sequencing and UHPLC‒QE‒MS. Women with a short cervix exhibited significant cervicovaginal microbiota dysbiosis, with an increased abundance of Ureaplasma and a decreased abundance of Lactobacillus , indicative of a CST IV profile. LEfSe analysis confirmed significant dysbiosis in the short cervix group, with Ureaplasma enrichment. Metabolomic and KEGG pathway analyses revealed high enrichment of the arachidonic acid metabolic pathway and a significant increase in its component 13,14-dihydro-15-ketoprostaglandin A2 in the short cervix group. Additionally, a strong positive correlation between Ureaplasma abundance and 13,14-dihydro-15-ketoprostaglandin A2 levels was observed. These biomarkers effectively distinguished sPTB at <34 weeks in women with a short cervix. Cervicovaginal microbiota dysbiosis and metabolic alterations might contribute to cervical shortening and sPTB risk, offering potential biomarkers and therapeutic targets for early intervention.