Spatial characterisation of the reproductive tract microbiota indicates high prevalence of microbial driven aetiology in preterm prelabour rupture of the fetal membranes (PPROM)

A high-diversity vaginal microbiome is a risk factor for preterm prelabour rupture of the fetal membranes (PPROM) and preterm birth, major causes of infant mortality and morbidity. Associative evidence supports a mechanism for preterm birth involving ascending vaginal pathogen infection and inflammation driving early labour. However, the relationship between the vaginal microbiome and upper reproductive tract colonisation in pregnancy remains poorly described. Using spatial metataxonomic characterisation of reproductive tract microbiota during pregnancy and delivery, we found higher bacterial load (p < 0.0001) and higher pathogen detection in fetal membranes (FM) from PPROM patients compared to term controls (12/15,80% v 9/24,38%; p < 0.01, χ2 test). FM levels of proinflammatory cytokines, MMP9 and complement system proteins were increased in PPROM, particularly in pathogen-enriched samples. Temporal and between-site comparison of strain-level data indicated the vagina as a likely source of upper reproductive tract pathogen colonisation in some cases. Our findings demonstrate that pathogen colonisation of the fetal membranes can occur in the presence of a Lactobacillus -dominated vaginal microbiome, suggesting pathogen driven PPROM is likely more common than previously acknowledged.