Bacterial community structure shapes the vaginal resistome during pregnancy

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Abstract Maternal-fetal infections are a leading cause of morbidity and mortality, often requiring complex antibiotic treatments due to increasing antibiotic resistance. However, the determinants of resistance in the vaginal microbiome (VMB) remain underexplored. We characterized a cohort of 1547 pregnant women and show that the VMB harbors a wide range of antibiotic resistance genes (ARGs). Genes conferring resistance to Macrolide-Lincosamide-Streptogramin (MLS) and tetracycline antibiotic classes were the most abundant, whereas those from ß-lactam class were the most diverse. ARG diversity was found to be primarily shaped by microbial community state types (CSTs), with CST I ( Lactobacillus crispatus-dominated community ) showing the lowest and CST IV ( anaerobic species-dominated community ) the highest diversity. Co-abundance patterns further revealed modular structures linking specific taxa (e.g., Gardnerella , Prevotella , and Enterobacterales ) to distinct ARGs and mobile genetic element profiles. A novel method incorporating predicted ARGs phenotypes, which we call the Phenotypic Resistance Diversity Index (PRDI), uncovered a resistome signature linked to adverse pregnancy outcomes, including increased microbial diversity and expanded predicted antibiotic resistance breadth in preterm premature rupture of membranes. Overall, our study establishes the VMB as a structured and dynamic reservoir of ARGs, contributing to the broader human resistome, opening new perspectives for advancing maternal and neonatal care.