Urinary Multiomics Signatures of Preterm Premature Rupture of Membranes: An Exploratory Analysis of Microbial and Metabolic Biomarkers

Preterm premature rupture of membranes (PPROM) is a significant obstetric complication, often associated with infection-related processes. However, the underlying mechanisms remain poorly understood, particularly regarding the interplay between microbial dysbiosis and host metabolism. To address this, urine samples from women with PPROM and healthy controls were analyzed using 16S rRNA gene sequencing and ¹H NMR-based metabolomics. Microbiota analysis revealed increased abundance of <i>Hoylesella</i>, <i>Escherichia</i>, <i>Pseudomonas</i>, and <i>Enterococcus</i> in the PPROM group, whereas <i>Lactobacillus</i> and <i>Limosilactobacillus</i> dominated in controls. Metabolomics identified key metabolites with diagnostic potential. Receiver operating characteristic (ROC) analysis showed that hippurate, formate, citrate, glycolate, serine, valine, and isoleucine had high discriminatory accuracy (AUC > 0.7), while β-glucose, asparagine, pyroglutarate, 2-hydroxyglutarate, tyrosine, creatinine, and imidazole had moderate predictive power. The PPROM group exhibited increased valine, isoleucine, asparagine, and β-glucose, while others decreased compared to controls. Multiomics integration revealed robust correlations between specific bacterial species and urinary metabolites, suggesting interactions between microbial dysbiosis and host metabolic pathways. These findings demonstrate distinct microbial and metabolic signatures in the urine of women with PPROM and support the utility of urinary multiomics analysis in advancing understanding of PPROM pathophysiology.