Vaginal dysbiosis and inflammatory signatures in preterm labor: an integrated model for predicting preterm birth.

Background: Preterm birth (PTB) is a major cause of neonatal morbidity and mortality, with vaginal microbiome dysbiosis and local immune responses implicated in its pathogenesis. However, the role of vaginal immune and extracellular matrix (ECM) remodeling factors in the progression from preterm labor (PTL) to PTB remains unclear. This study examines the associations between microbiome composition and immune and ECM-related protein composition in PTL patients to identify key factors and predictive models associated with the risk of PTB. Methods: This prospective study included 136 pregnant women classified into three groups: Control (Term Birth, TB), PTL-TB (Preterm Labor with Term Birth), and PTL-PTB (Preterm Labor with Preterm Birth). Vaginal microbiome composition was analyzed using 16S rRNA sequencing and categorized by dysbiosis status and community state types (CST). Cytokines (IL-1β, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70) and ECM remodeling enzymes (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, IGFBP-1) were quantified in vaginal secretions using the Luminex Results: Dysbiosis and CST IV were more prevalent in the PTL-PTB group. IL-1β was highest in CST III, while MMP-9 and other MMPs were elevated in CST IV. CVF MMP-9 was consistently increased across PTL-PTB cases, dysbiosis, and CST IV. However, IGFBP-1, MMP-8, and MMP-13 were significantly different by clinical outcome but not correlated with microbiome composition. A logistic regression model incorporating non-Lactobacillus fraction, IGFBP-1, MMP-9, MMP-13, and TNF-α demonstrated excellent predictive performance (AUC = 0.910) for PTB. Conclusions: Distinct microbial and immune profiles are associated with the progression from PTL to PTB. MMP-9 may serve as a key effector linking dysbiosis to extracellular matrix remodeling and PTB. Integrative biomarker models may support early risk stratification in women with PTL.