Integrated metagenomic and metabolomic profiling of spontaneous preterm birth in Chinese women

<h4>Background</h4>Spontaneous preterm birth (sPTB) remains a major cause of neonatal morbidity and mortality. We used integrated metagenomics and untargeted metabolomics to identify vaginal microbial and host metabolic signatures associated with sPTB in Chinese women.<h4>Methods</h4>Vaginal swabs (sPTB, <i>n</i> = 37; term, <i>n</i> = 62) and available maternal plasma were profiled by shotgun metagenomic sequencing and UHPLC-HRMS metabolomics. Group differences in microbial diversity/taxa and metabolite features were evaluated, followed by pathway enrichment and microbiome-metabolome correlation analyses.<h4>Results</h4>Compared with term controls, sPTB was characterized by reduced Lactobacillus dominance, higher vaginal microbial alpha diversity (<i>p</i> < 0.05), and distinct community structure (PERMANOVA <i>p</i> < 0.001). Metabolomic profiles of plasma and vaginal fluid differentiated sPTB from term pregnancy and highlighted decreased pantothenic acid and increased 4-pyridoxic acid, together with lipid and amino-acid perturbations. Pantothenic acid showed good discrimination (AUC = 0.82), and a multi-metabolite model improved classification (AUROC = 0.9544). KEGG analysis implicated vitamin B6 metabolism, pantothenate/CoA biosynthesis, and glycerophospholipid metabolism. Microbiome-metabolome integration dentified exploratory an sPTB-associated pattern in which Lactobacillus (e.g., <i>L. crispatus</i>) was positively correlated with pantothenic acid, while dysbiosis-/pathogen-associated taxa (including <i>C. trachomatis</i>) correlated with 4-pyridoxic acid.<h4>Conclusion</h4>sPTB in this Chinese cohort is associated with concurrent vaginal dysbiosis and systemic/local metabolic disturbances, supporting integrated microbiome-metabolite markers for risk stratification and potential preventive targets.