Longitudinal changes in the vaginal microbiome associate with spontaneous preterm birth: a focus on stability and specific taxa in a Chinese cohort

ABSTRACT Spontaneous preterm birth (sPTB) often results from ascending intra-amniotic infections originating from the vaginal microbiota. This study aimed to characterize vaginal microbial features and identify specific taxa associated with sPTB in a Chinese population. In this prospective cohort study, pregnant women were recruited from Peking Union Medical College Hospital. Vaginal swabs were collected longitudinally at 11–16, 22–28, and 34–37 weeks of gestation. DNA was analyzed using targeted real-time PCR (30 pathogens) and 16S rRNA gene sequencing (V3–V4). Community State Types (CSTs) were defined by enterotype-like clustering. Differential abundance was assessed using MaAsLin3 with Benjamini-Hochberg correction, adjusting for maternal age, BMI, and obstetric history. Among 273 women (26 sPTB, 247 term), no CST was significantly associated with sPTB after multivariable adjustment and false discovery rate (FDR) correction (all q > 0.05). Alpha and beta diversity also showed no significant between-group differences (all q > 0.05). However, longitudinal CST stability was significantly lower in the sPTB group ( P < 0.05). Nominally significant associations were observed for Ureaplasma urealyticum (first trimester), Mycoplasma hominis , and Bacteroides fragilis (second trimester), but none survived FDR correction (all q > 0.05). In this Chinese cohort, sPTB was not associated with static CST profiles but with reduced microbial stability over time. Although no single taxon remained significant after correction, several pathogens showed nominal associations, warranting further investigation in larger studies. IMPORTANCE Preterm birth (PTB) is a global maternal and infant health issue affecting approximately 11% of newborns worldwide. In China, the prevalence of PTB was 6.1%. Abnormal vaginal microbiota has been demonstrated to be a risk factor for PTB. Our study is one of the largest studies performed to date to investigate the associations between vaginal microbiome and spontaneous PTB (sPTB) in the Chinese cohort. We found that vaginal microbiome dynamics changes in Community State Types (CSTs) were significantly associated with sPTB. Furthermore, we also found that the microbial risk for sPTB appeared to be the enrichment of specific taxa, suggesting that vaginal dynamics and fine-scale features are important factors to consider in future studies.