How Does Microbial Community Composition and Metabolism Influence Inflammation-Induced Preterm Birth?

Preterm birth (PTB) is a global issue which effects more than 14 million babies per year resulting in increased infant mortality and lifelong diseases. The vaginal microbiome (VMB) has been associated with PTB and preterm prelabour rupture of fetal membranes (PPROM) however, the mechanisms remain unclear. Key bacteria such as Streptococcus agalactiae (GBS) and Gardnerella vaginalis have been extensively studied however there are many other bacteria commonly present in the vaginal microbial community which remain relatively unstudied. Currently prediction of which women will deliver prematurely (<37 weeks gestation) is limited. This study aimed to identify reliable predictive biomarkers of preterm birth from the vaginal microbiome (chapter 2), metabolome (chapter 3) and their interactions. Additionally, we aimed to assess how the VMB may play a role in PPROM through fetal membrane degradation via bacterial products (chapter 4). We were able to successfully optimise dynamic shear analysis, a novel technique for the study of fetal membrane integrity. We observed that infection-associated molecules reduced the visco-elastic properties of fetal membrane samples which may increase risk of PPROM in vivo. Additionally, we were able to characterise the cervico-vaginal microbiome and metabolome of asymptomatic women with and without sPTB. We identified bacteria and metabolites which are promising biomarkers for the prediction of PTB. Atopobium vaginae, Gardnerella vaginalis were found to be predictive of PTB at gestational timepoint (GTP) 1. At GTP2 pantothenate and phytoene were predictive of PTB. The change in abundance from GTP1 to GTP2 was also found to be predictive of PTB for pantothenate, phytoene, adenosine, dehydrosafynol, giganin, nonacosane and urate.