Alterations of the vaginal microbiome in healthy pregnant women positive for group B Streptococcus colonization during the third trimester

Abstract

Background: Streptococcus agalactiae or group B Streptococcus (GBS) asymptomatically colonizes the genitourinary tracts of up to 30% of pregnant women. Globally, GBS is an important cause of neonatal morbidity and mortality. GBS has recently been linked to adverse pregnancy outcomes. The potential interactions between GBS and the vaginal microbiome composition remain poorly understood. In addition, little is known about the vaginal microbiota of pregnant Egyptian women.

Results: Using V3-V4 16S rRNA next-generation sequencing, we examined the vaginal microbiome in GBS culture-positive pregnant women (22) and GBS culture-negative pregnant women (22) during the third trimester in Ismailia, Egypt. According to the alpha-diversity indices, the vaginal microbiome of pregnant GBS culture-positive women was significantly more diverse and less homogenous. The composition of the vaginal microbiome differed significantly based on beta-diversity between GBS culture-positive and culture-negative women. The phylum Firmicutes and the family Lactobacillaceae were significantly more abundant in GBS-negative colonizers. In contrast, the phyla Actinobacteria, Tenericutes, and Proteobacteria and the families Bifidobacteriaceae, Mycoplasmataceae, Streptococcaceae, Corynebacteriaceae, Staphylococcaceae, and Peptostreptococcaceae were significantly more abundant in GBS culture-positive colonizers. On the genus and species levels, Lactobacillus was the only genus detected with significantly higher relative abundance in GBS culture-negative status (88%), and L. iners was the significantly most abundant species. Conversely, GBS-positive carriers exhibited a significant decrease in Lactobacillus abundance (56%). In GBS-positive colonizers, the relative abundance of the genera Ureaplasma, Gardnerella, Streptococcus, Corynebacterium, Staphylococcus, and Peptostreptococcus and the species Peptostreptococcus anaerobius was significantly higher. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to the metabolism of cofactors and vitamins, phosphatidylinositol signaling system, peroxisome, host immune system pathways, and host endocrine system were exclusively enriched among GBS culture-positive microbial communities. However, lipid metabolism KEGG pathways, nucleotide metabolism, xenobiotics biodegradation and metabolism, genetic information processing pathways associated with translation, replication, and repair, and human diseases (Staphylococcus aureus infection) were exclusively enriched in GBS culture-negative communities.

Conclusions: Understanding how perturbations of the vaginal microbiome contribute to pregnancy complications may result in the development of alternative, targeted prevention strategies to prevent maternal GBS colonization. We hypothesized associations between inferred microbial function and GBS status that would need to be confirmed in larger cohorts.

Keywords: Group B Streptococcus; Healthy; Microbiome; Pregnant; Streptococcus agalactiae; Third trimester; Vagina.

Fig. 1

Relative abundance of the 10 top vaginal bacterial community genera in pregnant Egyptian women during the third trimester according to GBS status using SILVA database. A Relative abundance of vaginal genera in GBS culture-negative pregnant women. B Relative abundance of vaginal genera in GBS culture-positive pregnant carriers

Fig. 2

Taxa level relative abundance in vagina of pregnant Egyptian women during the third trimester according to GBS status using SILVA database. A Stacked bar charts represent relative proportions of the 10 most predominant genera in the vaginal microbiome of GBS culture-negative pregnant women (left) and GBS culture-positive pregnant carriers (right). B Stacked bar charts represent relative proportions of the 10 most predominant species in the vaginal microbiome of GBS culture-negative pregnant women (left) and GBS culture-positive pregnant carriers (right). Each bar represents one sample

Fig. 3

Linear discriminant analysis (LDA) effect size (LEfSe) biomarker analysis showing biomarker phylum (A), family (B), genus (C), and species (D) with significant differential abundance in GBS culture-negative and GBS culture-positive pregnant Egyptian women using SILVA database. FDR adjusted p values and LDA score > 2 was considered statistically significant. Not_Assigned refers to taxa that were challenging for biological interpretation

Fig. 4

Linear discriminant analysis (LDA) effect size (LEfSe) biomarker analysis showing biomarker phylum (A), family (B), genus (C), and species (D) with significant differential abundance in GBS culture-negative and GBS culture-positive pregnant Egyptian women using Greengenes database. FDR adjusted p values and LDA score > 2 was statistically significant. Not_Assigned refers to taxa that were challenging for biological interpretation

Fig. 5

Linear discriminant analysis (LDA) effect size (LEfSe) analysis of differentially abundant pathways between GBS-positive (green) and GBS-negative (red) bacterial communities during the third trimester of pregnancy in Egypt. LDA scores > 2 were considered statistically significant