The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions

From BugSigDB
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Mitra A, MacIntyre DA, Ntritsos G, Smith A, Tsilidis KK, Marchesi JR, Bennett PR, Moscicki AB, Kyrgiou M
Journal
Nature communications
Year
2020
Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16-26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.

Experiment 1


Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Subjects

Location of subjects
United States of America
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
Uterine cervix Canalis cervicis uteri,Caudal segment of uterus,Cervical canal,Cervical canal of uterus,Cervix,Cervix of uterus,Cervix uteri,Neck of uterus,Uterine cervix,uterine cervix
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Cervical glandular intraepithelial neoplasia Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
CIN regression
Group 1 name Corresponds to the case (exposed) group for case-control studies
CIN non-regression
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histology proven CIN2, no regression after 12 months
Group 0 sample size Number of subjects in the control (unexposed) group
42
Group 1 sample size Number of subjects in the case (exposed) group
45

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V2
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
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Figure 5

Description: LEfSe analysis identified baseline vaginal microbiota biomarkers associated with clinical outcomes at 12 months follow-up

Abundance in Group 1: increased abundance in CIN non-regression

NCBI Quality ControlLinks
Hoylesella timonensis
Negativicutes
Selenomonadales
Coriobacteriales
Eubacteriales
Atopobium
Fannyhessea vaginae
Coriobacteriaceae
Fusobacteriota
Sneathia
Leptotrichiaceae
Veillonellaceae
Megasphaera
Fusobacteriia
Fusobacteriales
Parvimonas
Clostridia
Lachnospiraceae
Prevotella
Bacteroidota
Bacteroidia
Prevotellaceae
Bacteroidales
Actinomycetes

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Figure 5

Description: LEfSe analysis identified baseline vaginal microbiota biomarkers associated with clinical outcomes at 12 months follow-up

Abundance in Group 1: decreased abundance in CIN non-regression

NCBI Quality ControlLinks
Lactobacillales
Bacilli
Lactobacillaceae
Lactobacillus
Bacillota

Revision editor(s): WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2021/07/16

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
Welch's T-Test
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Figure 4

Description: Outcomes at 12-month follow-up according to baseline VMB composition at baseline

Abundance in Group 1: increased abundance in CIN non-regression

NCBI Quality ControlLinks
Hoylesella timonensis
Gardnerella vaginalis

Revision editor(s): WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Fatima on 2021/07/16

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histology proven CIN2, no regression after 24 months
Group 0 sample size Number of subjects in the control (unexposed) group
63
Group 1 sample size Number of subjects in the case (exposed) group
24

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Supplementary Figure 2

Description: Outcomes at 24 month follow-up according to baseline VMB composition at baseline

Abundance in Group 1: increased abundance in CIN non-regression

NCBI Quality ControlLinks
Gardnerella vaginalis
Hoylesella timonensis

Revision editor(s): WikiWorks

Experiment 4


Reviewed Marked as Reviewed by Fatima on 2021/07/16

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
histology proven CIN2, no regression after 24 months among women with no regression after 12 months
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
14

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Supplementary Figure 3

Description: Supplementary Figure 3. Outcomes at 24 months according to VMB composition at 12 months in a subgroup of 35 women with ongoing disease

Abundance in Group 1: increased abundance in CIN non-regression

NCBI Quality ControlLinks
Aerococcus christensenii

Revision editor(s): WikiWorks