Integrated Metagenomic and Metabolomic Profiling of Spontaneous Preterm Birth in Chinese Women

Zhaodong Liu^1*Mian Pan^1*Heng Xue¹Yao Tang¹Wu Huang¹Xingliang Yu²Jun Zhang¹

• ¹Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
• ²Fujian Medical University School of Medical Technology and Engineering, Fuzhou, China

Background: 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. Methods: Vaginal swabs (sPTB, n=37; term, n=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. Spontaneous preterm birth (sPTB) is a leading cause of neonatal morbidity and mortality worldwide. Alterations in the maternal vaginal microbiome and host metabolism are increasingly recognized as contributors. We integrated metagenomic and metabolomic profiling in Chinese women to characterize microbial and metabolic perturbations associated with sPTB. 删除[author]: Vaginal swabs and maternal plasma from women with sPTB (n=37) and term controls (n=62) underwent shotgun metagenomic sequencing and untargeted metabolomics. Microbial diversity and taxonomic composition were compared. Metabolomic data were analyzed by PCA, PLS-DA, ROC, and random forest modeling. Pathway enrichment and microbiome–metabolome correlations were assessed. 删除[author]: Results: Compared with term controls, sPTB was characterized by reduced Lactobacillus dominance, higher vaginal microbial alpha diversity (P<0.05), and distinct community structure (PERMANOVA P<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., L. crispatus) was positively correlated with pantothenic acid, while dysbiosis-/pathogen-associated taxa (including C. trachomatis) correlated with 4-pyridoxic acid. Conclusions: 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.