Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth

Abstract

Background: The bacterial community present in the female lower genital tract plays an important role in maternal and neonatal health. Imbalances in this microbiota have been associated with negative reproductive outcomes, such as spontaneous preterm birth (sPTB), but the mechanisms underlying the association between a disturbed microbiota and sPTB remain poorly understood. An intrauterine infection ascending from the vagina is thought to be an important contributor to the onset of preterm labour. Our objective was to characterize the vaginal microbiota of pregnant women who had sPTB (n = 46) and compare to those of pregnant women who delivered at term (n = 170). Vaginal swabs were collected from women at 11-16 weeks of gestational age. Microbiota profiles were created by PCR amplification and pyrosequencing of the cpn60 universal target region.

Results: Profiles clustered into seven community state types: I (Lactobacillus crispatus dominated), II (Lactobacillus gasseri dominated), III (Lactobacillus iners dominated), IVA (Gardnerella vaginalis subgroup B or mix of species), IVC (G. vaginalis subgroup A dominated), IVD (G. vaginalis subgroup C dominated) and V (Lactobacillus jensenii dominated). The microbiota of women who experienced preterm birth (< 37 weeks gestation) had higher richness and diversity and higher Mollicutes prevalence when compared to those of women who delivered at term. The two groups did not cluster according to CST, likely because CST assignment is driven in most cases by the dominance of one particular species, overwhelming the contributions of more rare taxa. In conclusion, we did not identify a specific microbial community structure that predicts sPTB, but differences in microbiota richness, diversity and Mollicutes prevalence were observed between groups.

Conclusions: Although a causal relationship remains to be determined, our results confirm previous reports of an association between Mollicutes and sPTB and further suggest that a more diverse microbiome may be important in the pathogenesis of some cases.

Keywords: CST; Diversity; Infection; Lactobacillus; Microbiome; Mollicutes; Pregnancy; Preterm birth; Richness; Vagina.

Fig. 1

Vaginal microbiota profiles of women who had sPTB and term deliveries. a Hierarchical clustering of Jensen–Shannon distance matrices with Ward linkage on the relative proportions of reads for each OTU within individual vaginal samples. b Community state type (CST). c Gestational age at delivery. d Heatmap of relative abundances of bacterial species within each vaginal microbiota. Each column represents a woman’s vaginal microbiota profile, and each row represents a bacteria species. Only species that are at least 1% abundant in at least one sample are shown. e Shannon diversity indices calculated for each sample

Fig. 2

Vaginal microbiota profiles coloured by gestational age at delivery or CST. Jackknifed principal coordinates analysis (PCoA) of Bray–Curtis distance matrices of microbial profiles from all participants in the study

Fig. 3

Bacteria relative abundance differences between term and preterm groups represented by ALDEx2. a ALDEx2 between- and within-difference values for individual organisms across gestational age category. Organisms (at OTU and nearest neighbour species level) with significant p values are shown as pink circles (Welch’s t statistical test). b Violin plots showing the bacteria relative abundance (centre log transformed, CLR) in term and preterm groups. Only the eight bacteria with significant relative abundance differences between term and preterm groups are shown. In the violin plots, the white dot represents the median value, the black bar is the interquartile range, and the vertical width of the plot shows the density of the data along the X-axis