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Pregnancy Microbiomes Vary With Time, Body Site, Disease

NEW YORK (GenomeWeb) – Maternal microbial communities may vary over the course of pregnancy, by the body site considered, and with certain complications, according to a study published online today in Genome Research.

Researchers from Stanford University, Veterans Affairs Palo Alto Health Care System, and elsewhere used metagenomic sequencing to profile microbial community members and gene content in vaginal, gut, and mouth samples which had been previously collected from pregnant women for a study published in 2015. In addition to finding new microbial taxa, they produced draft genome assemblies for 97 microbes in vaginal samples, including assemblies for disease-related species or strains.

The team also began teasing out microbial diversity dynamics at each body site over the course of pregnancy, searching for microbes related to gestation time or birth complications. In the oral cavity and gut, for example, the results pointed to microbial shifts that coincided with the presence of preeclampsia.

"This work underscores the dynamic behavior of the microbiome during pregnancy and suggests the potential importance of understanding the sources of this behavior for fetal development and gestational outcome," senior author David Relman, a prematurity, microbiology and immunology, and infectious diseases researcher affiliated with Stanford and the VA Palo Alto Health Care System, and his colleagues wrote.

The samples — which were profiled with 16S ribosomal RNA gene sequencing for a study that some members of the same team published in the Proceedings of the National Academy of Sciences in 2015 — were collected from the mouths, guts, and vaginas of 10 pregnant women every three weeks, on average, from the first trimester to delivery.

In an effort to understand how the microbiome may reflect or even affect events taking place during pregnancy, the researchers used shotgun metagenomic sequencing to analyze the 292 samples for their current study. Four of the women delivered preterm, they noted, and five of the women experienced pregnancy complications such as preeclampsia or type 2 diabetes.

The researchers' analyses — including metagenomic sequence-based 16S reconstructions — revealed more than 22,700 predicted protein-coding genes and some 1,553 microbial taxa, occurring in communities that varied in their composition and diversity over time and by sampling site.

In the vaginal microbiome, the team noted that certain individual organisms tended to overshadow other microbial representatives. The vaginal microbiomes dominated by the Lactobacillus iners species typically showed enhanced microbial diversity as pregnancy progressed, for example, while vaginal microbiomes where L. crispatus was prominent remained more stable.

The overall diversity in oral and gut microbiomes usually remained stable as well, the researchers found, though the precise community compositions varied with time. They also noted that three women with preeclampsia had oral and gut microbiomes that clustered apart from those sampled in unaffected women.

Further, the researchers were able to put together draft genomes for half a dozen strains of Gardnerella vaginalis, a species previously implicated in pre-term birth that turned up at high levels in vaginal samples collected in early pregnancy from two of the participants who did go on to deliver prematurely. When the team compared those sequences with one another and with 34 full or partial G. vaginalis genomes from GenBank, it tracked down five distinct clades.

Moreover, with draft genome assemblies for these and other microbes, the researchers got a look at the gene repertoires and functional pathways available to microbial communities at the three body sites over different stages of pregnancy.

"Not surprisingly, core metabolic pathways consistently accounted for most of the overall pathway composition and abundance in all subjects," the authors wrote, adding that while individual pathway abundance was fairly stable, "some pathways were variable over gestational age."

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