Lactobacillus iners–Centered Vaginal Microbiota Modules in Early Pregnancy and Risk of Perinatal Complications

Abstract Perinatal complications such as spontaneous preterm birth, preterm premature rupture of membranes, cervical insufficiency, and recurrent miscarriage may share disruption of the cervical-vaginal ecosystem. We investigated whether network-level characterization of the early-pregnancy vaginal microbiota was associated with subsequent perinatal complications. In this single-center observational cohort study, vaginal swabs were collected at 8–12 weeks of gestation from 113 pregnant women. Species-level 16S rRNA sequencing showed high concordance with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, exceeding 82.4% for the most abundant species and reaching 100% when the two most abundant species were considered. Hierarchical clustering identified one Lactobacillus-dominant group and four anaerobe-dominant subgroups. In the most dysbiotic subgroup, characterized by Gardnerella, Fannyhessea, and Megasphaera, the only detectable Lactobacillus species was Lactobacillus iners. Co-occurrence network analysis further placed L. iners in the same module as bacterial vaginosis-associated taxa, distinct from Lactobacillus crispatus. This L. iners/bacterial vaginosis-associated module was significantly associated with recurrent miscarriage and spontaneous preterm birth, whereas the L. crispatus-centered module tended to be enriched in women without complications. These findings support network-based vaginal microbiota assessment in early pregnancy as a potential tool for identifying women at increased risk of subsequent perinatal complications.