Blood Microbial Communities During Pregnancy Are Associated With Preterm Birth

Abstract

Microbial infection of the placenta, amniotic fluid, vaginal canal, and oral cavity is known to significantly contribute to preterm birth (PTB). Although microbes can be translocated into the blood, little is known regarding the blood microbiota during pregnancy. To assess changes in the microbiome during pregnancy, blood samples were obtained 2 or 3 times during pregnancy from a cohort of 45 pregnant women enrolled between 2008 and 2010. To analyze the association with PTB, we conducted a case-control study involving 41 pregnant women upon admission for preterm labor and rupture of membrane (20 with term delivery; 21 with PTB). Bacterial diversity was assessed in number and composition between the first, second, and third trimesters in term delivered women according to 16S rRNA gene amplicon sequencing, and data were analyzed using Quantitative Insight Into Microbial Ecology (QIIME). Taxonomy was assigned using the GreenGenes 8.15.13 database. Dominant microorganisms at the phylum level in all pregnant women were identified as Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. However, the number and composition of bacteria in women with PTB differed from that in women with term delivery. Firmicutes and Bacteroidetes were more abundant in women with PTB than in women with term delivery, while Proteobacteria was less prevalent in women with PTB. At the genus level, Bacteroides, Lactobacillus, Sphingomonas, Fastidiosipila, Weissella, and Butyricicoccus were enriched in PTB samples. These observational results suggest that several taxa in the maternal blood microbiome are associated with PTB. Further studies are needed to confirm the composition of the blood microbiota in women with PTB. Additionally, the mechanism by which pathogenic microbes in maternal blood cause infection and PTB requires further analysis.

Keywords: 16S rRNA gene sequencing; blood microbiota; microbiome; pregnancy; preterm birth.

FIGURE 1

Microbial diversity and profiling during healthy pregnancy by 16S rRNA gene sequencing. (A) Comparison of Shannon index (community richness) in first, second, and third trimesters in maternal blood. (B) Plot of principal component analysis. Relative abundances of operational taxonomic units (OTUs) accounting for >0.1% of the total bacterial community are shown. (C) Bacterial profiling plot of relative abundances of OTUs at the phylum level and (D) genus level.

FIGURE 2

Differences in microbial diversity between term and preterm delivery. (A) Comparison of Shannon index (community richness) between term and preterm delivery (p = 2.02E-10). (B) Plot of principal component analysis. Relative abundances of operational taxonomic units (OTUs) accounting for >0.1% of the total bacterial community are shown.