Longitudinal study of the vaginal microbiome in pregnancies involving preterm labor

Abstract

Objectives: Alterations in the vaginal bacterial flora reflect the status of various obstetric conditions and are associated with mechanisms that underlie certain pregnancy-associated complications. These changes are also a predictive biomarker for clinical outcomes of these adverse events.

Methods: We examined the vaginal microbiome in samples from pregnant Japanese women with preterm labor.

Results: The microbiota composition in preterm delivery (PD) samples differed from those of control or threatened preterm delivery (TPD) samples in principal component analysis. An increase in Firmicutes and a decrease in Actinobacteria were significantly associated with PD only (both P<0.01). In the Firmicutes phylum, Lactobacillus tended to be abundant, and the abundance of L. iners and L. crispatus was especially high, whereas the L. gasseri population was low in PD samples. Longitudinal analysis showed that the abundance of L. iners decreased after commencing tocolytic treatment in TPD samples compared with before treatment, but it remained high in PD samples.

Conclusions: The vaginal microbiome may be a useful prognostic indicator of preterm labor and a monitoring tool for tocolytic treatment to prevent preterm birth.

Keywords: Lactobacillus iners; Preterm delivery; Vaginal microbiome.

Figure 1

Comparative analysis of vaginal microbiome profiles between the PD and TPD or control groups. A. Alpha diversity of the vaginal microbiome. The rare fraction curve was constructed using weighted UniFrac analysis. Red lines indicate the PD group and blue lines indicate the TPD and control groups. B. A PCA plot was constructed using weighted UniFrac analysis. Red, green, and blue circles indicate the PD, TPD, and control groups, respectively.

Figure 2

Relative abundance of different bacterial phyla in each sample. The seven most abundant bacterial phyla are indicated. One-way analysis of variance was performed for comparison between each group. Firmicutes: controls vs TPD, P=0.84; TPD vs PD, P=0.005; controls vs PD, P=0.0001. Actinobacteria: controls vs TPD, P=0.87; TPD vs PD, P=0.01; controls vs PD, P=0.001. Proteobacteria: controls vs TPD, P=0.61; TPD vs PD, P=0.65; controls vs PD, P=0.15.

Figure 3

Volcano plot of the relative abundance of each bacterial genus. The x-axis indicates the fold changes of genera in PD samples compared with non PD samples, while the y-axis indicates P values. A. Finegoldia (20-fold, P=0.17); B. Lactobacillus (2-fold, P=0.10); and C. Bifidobacterium (0.02-fold, P=0.46).

Figure 4

Comparative analysis of the relative abundance of Lactobacillus strains in the vaginal microbiome between the PD and non PD groups. A. Lactobacillus genus; B. L. iners; C. L. crispatus; and D. L. gasseri.

Figure 5

Longitudinal analysis of the abundance of strains of the Lactobacillus genus in the vaginal microbiome in the TPD group. The relative abundance of Lactobacillus was compared between pre- and post-tocolytic treatment for premature labor. A. Lactobacillus genus; B. L. crispatus; and C. L. iners. We also calculated the post- to pre-treatment ratio for the abundance of L. iners in the PD, TPD, and control groups.