skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Genome Research
 [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)

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1506368
Journal Information:
Genome Research, Vol. 28, Issue 10; ISSN 1088-9051
Publisher:
Cold Spring Harbor Laboratory PressCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 83 works
Citation information provided by
Web of Science

References (91)

Temporal Dynamics of the Human Vaginal Microbiota journal May 2012
Comparative Genomics of Gardnerella vaginalis Strains Reveals Substantial Differences in Metabolic and Virulence Potential journal August 2010
An updated evolutionary classification of CRISPR–Cas systems journal September 2015
UCHIME improves sensitivity and speed of chimera detection journal June 2011
Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements journal February 2005
Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy journal August 2012
Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women journal August 2017
Geneious Basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data journal April 2012
UniProt: the universal protein knowledgebase journal November 2016
Comparative genomics of Lactobacillus crispatus suggests novel mechanisms for the competitive exclusion of Gardnerella vaginalis journal January 2014
Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya journal January 2016
Ecological Role of Lactobacilli in the Gastrointestinal Tract: Implications for Fundamental and Biomedical Research journal June 2008
Role of Gardnerella vaginalis in the Pathogenesis of Bacterial Vaginosis: A Conceptual Model journal February 2014
Changes in vaginal community state types reflect major shifts in the microbiome journal January 2017
KAAS: an automatic genome annotation and pathway reconstruction server journal May 2007
Homeostasis and Inflammation in the Intestine journal March 2010
The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women journal February 2014
Major bacterial lineages are essentially devoid of CRISPR-Cas viral defence systems journal February 2016
Fast and accurate short read alignment with Burrows-Wheeler transform journal May 2009
The vaginal microbiome during pregnancy and the postpartum period in a European population journal March 2015
KEGG: Kyoto Encyclopedia of Genes and Genomes journal January 2000
At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1 journal November 2010
The Application of Ecological Theory Toward an Understanding of the Human Microbiome journal June 2012
Community-wide analysis of microbial genome sequence signatures journal January 2009
Lactobacillus rhamnosus L60, a potential probiotic isolated from the human vagina journal January 2008
Diverse CRISPRs Evolving in Human Microbiomes journal June 2012
Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time journal December 2010
EMIRGE: reconstruction of full-length ribosomal genes from microbial community short read sequencing data journal May 2011
Genomes of Gardnerella Strains Reveal an Abundance of Prophages within the Bladder Microbiome journal November 2016
Early pregnancy vaginal microbiome trends and preterm birth journal September 2017
tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence journal March 1997
Association between Bacterial Vaginosis and Preterm Delivery of a Low-Birth-Weight Infant journal December 1995
Prodigal: prokaryotic gene recognition and translation initiation site identification journal March 2010
CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea journal February 2010
Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women journal May 2007
DECIPHER, a Search-Based Approach to Chimera Identification for 16S rRNA Sequences journal November 2011
Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems journal November 2015
The vaginal microbiota, host defence and reproductive physiology: Vaginal microbiota in defence and physiology journal May 2016
Search and clustering orders of magnitude faster than BLAST journal August 2010
Virus Population Dynamics and Acquired Virus Resistance in Natural Microbial Communities journal May 2008
kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome: Table 1 journal April 2015
VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing journal February 2012
phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data journal April 2013
Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study journal June 2018
Diversity of the Vaginal Microbiome Correlates With Preterm Birth journal May 2013
progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement journal June 2010
IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth journal April 2012
Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome journal June 2012
Vaginal microbiome of reproductive-age women journal June 2010
SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB journal November 2007
Unusual biology across a group comprising more than 15% of domain Bacteria journal June 2015
Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes and exhibit different in situ growth rates journal January 2017
Vaginal Microbiome: Rethinking Health and Disease journal October 2012
Understanding vaginal microbiome complexity from an ecological perspective journal October 2012
Role of the gut microbiota in defining human health journal April 2010
CRISPR/Cas, the Immune System of Bacteria and Archaea journal January 2010
Fast gapped-read alignment with Bowtie 2 journal March 2012
A new view of the tree of life journal April 2016
Enterobactin: An archetype for microbial iron transport journal March 2003
The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes journal November 2014
The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk journal January 2017
The CRISPR System: Small RNA-Guided Defense in Bacteria and Archaea journal January 2010
Gardnerella vaginalis comprises three distinct genotypes of which only two produce sialidase journal May 2011
Bellerophon: a program to detect chimeric sequences in multiple sequence alignments journal April 2004
MUSCLE: multiple sequence alignment with high accuracy and high throughput journal March 2004
bioDBnet: the biological database network journal January 2009
FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix journal April 2009
Temporal and spatial variation of the human microbiota during pregnancy journal August 2015
A microbial perspective of human developmental biology journal July 2016
Metagenomic reconstructions of bacterial CRISPR loci constrain population histories journal September 2015
Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions journal April 2013
The human microbiome: at the interface of health and disease journal March 2012
Crass: identification and reconstruction of CRISPR from unassembled metagenomic data journal March 2013
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 journal December 2014
Human oral viruses are personal, persistent and gender-consistent journal March 2014
Association between living environment and human oral viral ecology journal April 2013
Microbial Changes during Pregnancy, Birth, and Infancy journal July 2016
The association between vaginal microbiota and female infertility: a systematic review and meta-analysis journal July 2020
Coriander Genomics Database: a genomic, transcriptomic, and metabolic database for coriander journal April 2020
Microbial community structure and functional properties in permanently and seasonally flooded areas in Poyang Lake journal March 2020
The Sequence Alignment/Map format and SAMtools journal June 2009
UniProt: the Universal Protein knowledgebase journal January 2004
Fine-scale population structure and evidence for local adaptation in Australian giant black tiger shrimp (Penaeus monodon) using SNP analysis journal September 2020
Datura genome reveals duplications of psychoactive alkaloid biosynthetic genes and high mutation rate following tissue culture journal March 2021
CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes journal May 2015
Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. text January 2012
BLAST+: architecture and applications journal January 2009
"Association between Bacterial Vaginosis and Preterm Delivery of a Low- birth-weight Infant." journal January 1996
tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence journal March 1997
Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. text January 2012
UniProt: the universal protein knowledgebase journal February 2018

Cited By (9)

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women journal May 2019
Multiomic immune clockworks of pregnancy journal February 2020
A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina journal February 2020
Racioethnic diversity in the dynamics of the vaginal microbiome during pregnancy journal May 2019
Computational Framework for High-Quality Production and Large-Scale Evolutionary Analysis of Metagenome Assembled Genomes journal October 2019
Understanding and interpreting community sequencing measurements of the vaginal microbiome journal November 2019
Association between gut microbiota composition and glycoalbumin level during pregnancy in Japanese women: Pilot study from Chiba Study of Mother and Child Health journal December 2019
High‐fat diet intake modulates maternal intestinal adaptations to pregnancy and results in placental hypoxia, as well as altered fetal gut barrier proteins and immune markers journal May 2019
Human and Extracellular DNA Depletion for Metagenomic Analysis of Complex Clinical Infection Samples Yields Optimized Viable Microbiome Profiles journal February 2019

Similar Records

Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents
Journal Article · Tue Nov 23 00:00:00 EST 2021 · Viruses · OSTI ID:1506368

Amylases in the Human Vagina
Journal Article · Wed Dec 09 00:00:00 EST 2020 · mSphere · OSTI ID:1506368

Dichotomous development of the gut microbiome in preterm infants
Journal Article · Wed Sep 12 00:00:00 EDT 2018 · Microbiome · OSTI ID:1506368

Related Subjects