Abstract
A major challenge in preventing preterm birth (PTB) is identifying women at greatest risk. This pilot study prospectively examined the differences in vaginal microbiota and metabolite profiles of women who delivered prematurely compared to their term counterparts in a cohort of asymptomatic (studied at 20–22, n = 80; and 26–28 weeks, n = 41) and symptomatic women (studied at 24–36 weeks, n = 37). Using 16S rRNA sequencing, the vaginal microbiota from cervicovaginal fluid samples was characterized into five Community State Types (CST) dominated by Lactobacillus spp.: CSTI (Lactobacillus crispatus), CSTII (Lactobacillus gasseri), CSTIII (Lactobacillus iners), CSTV (Lactobacillus jensenii); and mixed anaerobes—CSTIV. This was then related to the vaginal metabolite profile and pH determined by 1H-Nuclear Magnetic Resonance spectroscopy and pH indicator paper, respectively. At 20–22 weeks, the term-delivered women (TDW) indicated a proportion of CSTI-dominated microbiota >2-fold higher compared to the preterm-delivered women (PTDW) (40.3 vs. 16.7%, P = 0.0002), and a slightly higher proportion at 26–28 weeks (20.7 vs. 16.7%, P = 0.03). CSTV was >2-fold higher in the PTDW compared to TDW at 20–22 (22.2 vs. 9.7%, P = 0.0002) and 26–28 weeks (25.0 vs. 10.3%, P = 0.03). Furthermore, at 26–28 weeks no PTDW had a CSTII-dominated microbiome, in contrast to 28% of TDW (P < 0.0001). CSTI-dominated samples showed higher lactate levels than CSTV at 20–22 weeks (P < 0.01), and 26–28 weeks (P < 0.05), while CSTII-dominated samples indicated raised succinate levels over CSTV at 26–28 weeks (P < 0.05). These were supported by Principal coordinates analysis, which revealed strong clustering of metabolites according to CST. In addition, the CSTI-dominated samples had an average pH of 3.8, which was lower than those of CSTII—4.4, and CSTV—4.2 (P < 0.05). Elevated vaginal lactate and succinate were associated with predominance of CSTI and II over CSTV in women who delivered at term compared with their preterm counterparts. This suggests that L. jensenii-dominance and decreased lactate and/or succinate could increase the risk of PTB, while L. crispatus/gasseri may confer some protection against inflammation-associated PTB and highlight the need for further study in this area.
Highlights
Preterm birth (PTB) is the leading contributor to infant mortality and morbidity globally with associated multi-billion dollar health costs (MacDorman et al, 2007; Goldenberg et al, 2008; Blencowe et al, 2013a,b)
We highlight important links between microbial community state-types and targeted metabolite profiles in relation to PTB, thereby highlighting the potential functional and clinical significance of combining these determinations to improve our understanding of the mechanisms of inflammationassociated PTB
We show that community composition seems to differ between women who delivered at term and those who delivered preterm
Summary
Preterm birth (PTB) is the leading contributor to infant mortality and morbidity globally with associated multi-billion dollar health costs (MacDorman et al, 2007; Goldenberg et al, 2008; Blencowe et al, 2013a,b). While much study has focused on the causes and molecular mechanisms of PTB there are still major challenges in identifying which women who are at risk of PTB. In addition to a history of previous PTB, the increased expression of fetal fibronectin in cervicovaginal fluid and a short cervix on ultrasound are observations associated with risk of premature delivery (DeFranco et al, 2013). These tests have limited utility for accurate prediction of PTB, which occurs mostly in women with no apparent risk factors. Up to half of all PTBs, are associated with evidence of infection or inflammation in gestational tissue (Knox and Hoerner, 1950; Goldenberg et al, 2000)
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