Vaginal host immune-microbiome-metabolite interactions associated with spontaneous preterm birth in a predominantly white cohort
Megan Cavanagh, Emmanuel Amabebe, Neha Kulkarni, Μαρία Παπαγεωργίου, Heather Walker, Matthew D. Wyles, Dilly Anumba
Abstract
Abstract In order to improve spontaneous preterm birth (sPTB) risk stratification in a predominantly white cohort of non-labouring pregnant women, we analysed their vaginal microbiota, metabolite, cytokine and foetal fibronectin (FFN) concentrations at two gestational time points (GTPs): GTP1 (20 +0 –22 +6 weeks, preterm = 17; term = 32); and GTP2 (26 +0 –28 +6 weeks, preterm = 14; term = 31). At GTP1, the preterm-delivered women showed abundant G. vaginalis (AUC = 0.77) over L. crispatus and L. iners , and upregulation of 10 metabolites. At GTP2, the same women had more lactobacilli- and mixed anaerobes-dominated microbiota, upregulation of five metabolites, and decreased TNFR1, distinguishing them from their term counterparts (AUC = 0.88). From GTP1 to GTP2, sPTB was associated with increased microbiota α-diversity, and upregulation of pantothenate and urate. CXCL10 declined in the term-delivered women by ~3-fold, but increased in the preterm-delivered women (AUC = 0.68), enhanced by FFN (AUC = 0.74). Characterising the complex dynamic interactions between cervicovaginal microbial metabolites and host immune responses could enhance sPTB risk stratification.