Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome
- Daniela S. Aliaga Goltsman1,2,9,
- Christine L. Sun1,2,9,
- Diana M. Proctor3,4,
- Daniel B. DiGiulio1,3,4,
- Anna Robaczewska1,4,
- Brian C. Thomas5,
- Gary M. Shaw1,6,
- David K. Stevenson1,6,
- Susan P. Holmes7,
- Jillian F. Banfield5,8 and
- David A. Relman1,2,3,4
- 1March of Dimes Prematurity Research Center at Stanford University, Stanford, California 94305, USA;
- 2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;
- 3Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
- 4Infectious Diseases Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA;
- 5Department of Earth and Planetary Science, University of California, Berkeley, California 94720, USA;
- 6Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA;
- 7Department of Statistics, Stanford University, Stanford, California 94305, USA;
- 8Earth and Environmental Science, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
-
↵9 These authors contributed equally to this work.
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 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.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.236000.118.
- Received February 15, 2018.
- Accepted August 28, 2018.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
