78: Distinct alterations in the placental microbiome among spontaneous preterm births

Previously, we and others have shown that the vaginal and gut human microbiome (the totality of microbes and their genomes) are altered during pregnancy and vary further by gestational age. Similarly, we have recently demonstrated that the placenta harbors a low biomass microbiome which varies in association with spontaneous PTB (sPTB). Given inherent limitations to longitudinal placental collection in any given pregnancy, delineating causation from association is problematic. We reasoned that robust causal inference analysis across mutliple body sites in a prospective longitudinal cohort inclusive of both spontaneous and indicated PTB could potentially overcome such obstacles. Gravid subjects (n=277) were enrolled in the early 3rd trimester or at delivery (170 term, 107 preterm). Extensive clinical metadata (such as comorbidities and indications for induction) enabled covariate analytics and gestational age comparison. Oral, vaginal, stool and placental swabs & tissue were uniformly clean collected from subjects and their infants. DNA was extracted (MoBio) and subjected to 16S and whole genome shotgun (WGS) metagenomics. Quality filtered sequences were analyzed with customized tools (QIIME & MG-RAST) and causal inference approaches (hierarchical clustering by Manhattan distance & regression modeling). Consistent with recent findings, we did not detect likely causal differences in the posterior fornix of preterm subjects (p=0.254), but did observe significant variation in the placental microbiome (p=0.012; A left) which were attributable to cases of spontaneous PTB (A right, p=0.0323 PC2 axis). Moreover, significantly altered taxa abundance (including Mycoplasma & Fusobacterium; Fig.B) persisted amongst sPTB comparative of gestational age and covariates. Causal inference analysis in a longitudinal cohort enabled us to delineate a persistent and significant association of the placental microbiome with spontaneous PTB, which appears distinct from indicated births at akin gestational ages.