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Title: Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome

Abstract

Recent studies suggest that the microbiome has an impact on gestational health and outcome. However, characterization of the pregnancy-associated microbiome has largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and oral microbiomes in 292 samples from 10 subjects sampled every three weeks throughout pregnancy. Nonhuman sequences in the amount of 1.53 Gb were assembled into scaffolds, and functional genes were predicted for gene- and pathway-based analyses. Vaginal assemblies were binned into 97 draft quality genomes. Redundancy analysis (RDA) of microbial community composition at all three body sites revealed gestational age to be a significant source of variation in patterns of gene abundance. In addition, health complications were associated with variation in community functional gene composition in the mouth and gut. The diversity of Lactobacillus iners-dominated communities in the vagina, unlike most other vaginal community types, significantly increased with gestational age. The genomes of co-occurring Gardnerella vaginalis strains with predicted distinct functions were recovered in samples from two subjects. In seven subjects, gut samples contained strains of the same Lactobacillus species that dominated the vaginal community of that same subject and not other Lactobacillus species; however, these within-host strainsmore » were divergent. CRISPR spacer analysis suggested shared phage and plasmid populations across body sites and individuals. 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.« less

Authors:
 [1];  [1]; ORCiD logo [2];  [2];  [2];  [3];  [1];  [1];  [1];  [4]; ORCiD logo [2]
  1. Stanford Univ., CA (United States)
  2. Stanford Univ., CA (United States); Veterans Affairs Palo Alto Health Care System, Palo Alto, CA (United States)
  3. Univ. of California, Berkeley, CA (United States)
  4. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1506368
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Genome Research
Additional Journal Information:
Journal Volume: 28; Journal Issue: 10; Journal ID: ISSN 1088-9051
Publisher:
Cold Spring Harbor Laboratory Press
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Goltsman, Daniela S. Aliaga, Sun, Christine L., Proctor, Diana M., DiGiulio, Daniel B., Robaczewska, Anna, Thomas, Brian C., Shaw, Gary M., Stevenson, David K., Holmes, Susan P., Banfield, Jillian F., and Relman, David A. Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome. United States: N. p., 2018. Web. doi:10.1101/gr.236000.118.
Goltsman, Daniela S. Aliaga, Sun, Christine L., Proctor, Diana M., DiGiulio, Daniel B., Robaczewska, Anna, Thomas, Brian C., Shaw, Gary M., Stevenson, David K., Holmes, Susan P., Banfield, Jillian F., & Relman, David A. Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome. United States. doi:10.1101/gr.236000.118.
Goltsman, Daniela S. Aliaga, Sun, Christine L., Proctor, Diana M., DiGiulio, Daniel B., Robaczewska, Anna, Thomas, Brian C., Shaw, Gary M., Stevenson, David K., Holmes, Susan P., Banfield, Jillian F., and Relman, David A. Wed . "Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome". United States. doi:10.1101/gr.236000.118. https://www.osti.gov/servlets/purl/1506368.
@article{osti_1506368,
title = {Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome},
author = {Goltsman, Daniela S. Aliaga and Sun, Christine L. and Proctor, Diana M. and DiGiulio, Daniel B. and Robaczewska, Anna and Thomas, Brian C. and Shaw, Gary M. and Stevenson, David K. and Holmes, Susan P. and Banfield, Jillian F. and Relman, David A.},
abstractNote = {Recent studies suggest that the microbiome has an impact on gestational health and outcome. However, characterization of the pregnancy-associated microbiome has largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and oral microbiomes in 292 samples from 10 subjects sampled every three weeks throughout pregnancy. Nonhuman sequences in the amount of 1.53 Gb were assembled into scaffolds, and functional genes were predicted for gene- and pathway-based analyses. Vaginal assemblies were binned into 97 draft quality genomes. Redundancy analysis (RDA) of microbial community composition at all three body sites revealed gestational age to be a significant source of variation in patterns of gene abundance. In addition, health complications were associated with variation in community functional gene composition in the mouth and gut. The diversity of Lactobacillus iners-dominated communities in the vagina, unlike most other vaginal community types, significantly increased with gestational age. The genomes of co-occurring Gardnerella vaginalis strains with predicted distinct functions were recovered in samples from two subjects. In seven subjects, gut samples contained strains of the same Lactobacillus species that dominated the vaginal community of that same subject and not other Lactobacillus species; however, these within-host strains were divergent. CRISPR spacer analysis suggested shared phage and plasmid populations across body sites and individuals. 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.},
doi = {10.1101/gr.236000.118},
journal = {Genome Research},
issn = {1088-9051},
number = 10,
volume = 28,
place = {United States},
year = {2018},
month = {9}
}

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