Shotgun sequencing of the vaginal microbiome reveals both a species and functional potential signature of preterm birth
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Feehily C, Crosby D, Walsh CJ, Lawton EM, Higgins S, McAuliffe FM, Cotter PD
Journal
NPJ biofilms and microbiomes
Year
2020
An association between the vaginal microbiota and preterm birth (PTB) has been reported in several research studies. Population shifts from high proportions of lactobacilli to mixed species communities, as seen with bacterial vaginosis, have been linked to a twofold increased risk of PTB. Despite the increasing number of studies using next-generation sequencing technologies, primarily involving 16S rRNA-based approaches, to investigate the vaginal microbiota during pregnancy, no distinct microbial signature has been associated with PTB. Shotgun metagenomic sequencing offers a powerful tool to reveal community structures and their gene functions at a far greater resolution than amplicon sequencing. In this study, we employ shotgun metagenomic sequencing to compare the vaginal microbiota of women at high risk of preterm birth (n = 35) vs. a low-risk control group (n = 14). Although microbial diversity and richness did not differ between groups, there were significant differences in terms of individual species. In particular, Lactobacillus crispatus was associated with samples from a full-term pregnancy, whereas one community state-type was associated with samples from preterm pregnancies. Furthermore, by predicting gene functions, the functional potential of the preterm microbiota was different from that of full-term equivalent. Taken together, we observed a discrete structural and functional difference in the microbial composition of the vagina in women who deliver preterm. Importance: with an estimated 15 million cases annually, spontaneous preterm birth (PTB) is the leading cause of death in infants under the age of five years. The ability to accurately identify pregnancies at risk of spontaneous PTB is therefore of utmost importance. However, no single cause is attributable. Microbial infection is a known risk factor, yet the role of vaginal microbes is poorly understood. Using high-resolution DNA-sequencing techniques, we investigate the microbial communities present in the vaginal tracts of women deemed high risk for PTB. We confirm that Lactobacillus crispatus is strongly linked to full-term pregnancies, whereas other microbial communities associate with PTB. Importantly, we show that the specific functions of the microbes present in PTB samples differs from FTB samples, highlighting the power of our sequencing approach. This information enables us to begin understanding the specific microbial traits that may be influencing PTB, beyond the presence or absence of microbial taxa.
Experiment 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Subjects
- Location of subjects
- Ireland
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Posterior fornix of vagina , External cervical os Pars posterior fornicis vaginae,Posterior fornix,Posterior part of fornix of vagina,Posterior fornix of vagina,posterior fornix of vagina,External os,External os of uterus,Ostium of uterus,Ostium uteri,External cervical os,external cervical os
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Spontaneous preterm birth Spontaneous preterm birth,spontaneous preterm birth
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Full-term Birth
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Preterm Birth
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Pregnant women who delivered before 37 weeks’ gestation.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 41
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Women currently on antibiotic treatment.
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- T-Test
- Linear Regression
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.25
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Source: Figure 2b + Figure 2C
Description: Differentially abundant species for Preterm Birth (PTB) within the delivery outcome group compared to Full-term birth (FTB)
Abundance in Group 1: increased abundance in Preterm Birth
Revision editor(s): Joan Chuks, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Source: Figure 2b + Figure 2C
Description: Differentially abundant species for Preterm Birth (PTB) within the delivery outcome group compared to Full-term birth (FTB)
Abundance in Group 1: decreased abundance in Preterm Birth
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium breve | ||
| Lactobacillus crispatus | ||
| Lactobacillus gasseri ATCC 33323 = JCM 1131 | ||
| Lactobacillus johnsonii |
Revision editor(s): Joan Chuks, ChiomaBlessing
Experiment 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low-risk controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Risk Group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Pregnant women with either a history of previous spontaneous preterm birth (risk_PTB) or women with risk factors for preterm birth but who delivered full term (risk_FTB)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 14
- Group 1 sample size Number of subjects in the case (exposed) group
- 35
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Source: Figure 2C
Description: Differentially abundant species within the Risk group.
Abundance in Group 1: increased abundance in Risk Group
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium breve |
Revision editor(s): Joan Chuks
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Source: Figure 2C
Description: Differentially abundant species within the Risk group
Abundance in Group 1: decreased abundance in Risk Group
| NCBI | Quality Control | Links |
|---|---|---|
| Caloramator mitchellensis | ||
| Mycobacterium sp. 852013-50091_SCH5140682 | ||
| Stenotrophomonas maltophilia |
Revision editor(s): Joan Chuks
Experiment 3
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- No Previous Preterm birth
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Previous Preterm birth
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Pregnant women with a history of previous spontaneous preterm birth (PTB)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 29
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Source: Figure 2C
Description: Differentially abundant species for Previous Preterm birth(PTB) group
Abundance in Group 1: increased abundance in Previous Preterm birth
Revision editor(s): Joan Chuks
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
Source: Figure 2C
Description: Differentially abundant species for Previous Preterm birth(PTB) group
Abundance in Group 1: decreased abundance in Previous Preterm birth
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium breve | ||
| Bifidobacterium longum subsp. infantis |
Revision editor(s): Joan Chuks
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