Urinary Multi-Omics Signatures of Preterm Premature Rupture of Membranes: Insights into 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 Hoylesella, Escherichia, Pseudomonas, and Enterococcus in the PPROM group, whereas Lactobacillus and Limosilactobacillus 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 beta-glucose, asparagine, pyroglutarate, 2-hydroxyglutarate, tyrosine, creatinine, and imidazole had moderate predictive power. The PPROM group exhibited increased valine, isoleucine, asparagine, and beta-glucose, while others decreased compared to controls. Multi-omics 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 multi-omics analysis in advancing understanding of PPROM pathophysiology.