Shotgun metagenomics of the vaginal microbiome in cervical shortening and preterm birth risk

Preterm birth (PTB), a leading cause of neonatal morbidity and mortality, is frequently associated with premature cervical remodeling and vaginal microbiome dysbiosis. Cervical shortening in mid-pregnancy is a well-established risk factor for spontaneous PTB (sPTB), yet the microbial signatures underlying this condition remain underexplored, especially in Asian populations. In this study, we conducted shotgun metagenomic analysis of vaginal samples from 35 East Asian pregnant women with a short cervix and 12 with normal cervical length. Species-level taxonomic profiling and functional pathway analysis revealed reduced Lactobacillus dominance, increased microbial diversity, and enrichment of non-optimal CST IV species, such as Fannyhessea vaginae, Bifidobacterium breve, and Mycobacterium canetti in the short cervix group. Functional profiling showed group differences in pathways related to folate biosynthesis, carbohydrate metabolism, and epithelial barrier regulation. Among women with a short cervix, those who delivered preterm had vaginal microbiomes enriched in opportunistic pathogens, including Peptoniphilus equinus, Treponema spp., and Staphylococcus hominis. Conversely, B. breve, Lactobacillus gasseri, and Lactobacillus paragasseri were associated with full-term delivery. Functions related to glycosylation, structural stability, and degradation of cervical mucin were enriched in the sPTB group. Network analysis identified distinct microbial interactions between Lactobacillus-dominated clusters and CST IV-associated taxa, providing ecological insights that may reflect competitive dynamics and potential influences on cervicovaginal barrier integrity. These findings enhance our understanding of the taxonomic and functional profiles of the vaginal microbiome linked to cervical shortening and sPTB, contributing to improved risk stratification and management strategies for PTB, particularly in women with cervical shortening.