The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study

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Reviewed Marked as Reviewed by Atrayees on 2023-7-13
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Perrotta AR, Borrelli GM, Martins CO, Kallas EG, Sanabani SS, Griffith LG, Alm EJ, Abrao MS
Journal
Reproductive sciences (Thousand Oaks, Calif.)
Year
2020
Keywords:
Diagnosis, Endometriosis, Microbiome, Pathogenesis, Vaginal microbiome
Endometriosis remains a challenge to understand and to diagnose. This is an observational cross-sectional pilot study to characterize the gut and vaginal microbiome profiles among endometriosis patients and control subjects without the disease and to explore their potential use as a less-invasive diagnostic tool for endometriosis. Overall, 59 women were included, n = 35 with endometriosis and n = 24 controls. Rectal and vaginal samples were collected in two different periods of the menstrual cycle from all subjects. Gut and vaginal microbiomes from patients with different rASRM (revised American Society for Reproductive Medicine) endometriosis stages and controls were analyzed. Illumina sequencing libraries were constructed using a two-step 16S rRNA gene PCR amplicon approach. Correlations of 16S rRNA gene amplicon data with clinical metadata were conducted using a random forest-based machine-learning classification analysis. Distribution of vaginal CSTs (community state types) significantly differed between follicular and menstrual phases of the menstrual cycle (p = 0.021, Fisher's exact test). Vaginal and rectal microbiome profiles and their association to severity of endometriosis (according to rASRM stages) were evaluated. Classification models built with machine-learning methods on the microbiota composition during follicular and menstrual phases of the cycle were built, and it was possible to accurately predict rASRM stages 1-2 verses rASRM stages 3-4 endometriosis. The feature contributing the most to this prediction was an OTU (operational taxonomic unit) from the genus Anaerococcus. Gut and vaginal microbiomes of women with endometriosis have been investigated. Our findings suggest for the first time that vaginal microbiome may predict stage of disease when endometriosis is present.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-7-13

Curated date: 2021/08/09

Curator: Samara.Khan

Revision editor(s): Samara.Khan, WikiWorks, Atrayees

Subjects

Location of subjects
Brazil
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Vagina Distal oviductal region,Distal portion of oviduct,Vaginae,Vagina
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
endometriosis endometriosis,Endometriosis (clinical),endometriosis (disease),Endometriosis (disorder),Endometriosis (morphologic abnormality),ENDOMETRIOSIS NEC,Endometriosis NOS,Endometriosis NOS (disorder),Endometriosis of other specified sites,Endometriosis, site unspecified
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Stage 1/2 Endometriosis patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Stage 3/4 Endometriosis patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients were diagnosed with endometriosis via laparoscopic surgery and stages were categorized according to the revised American Society for Reproductive Medicine scoring system (r-ASRM). This study was comparing patients with different stages of endometriosis to each other.
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
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Participants were excluded if they had taken antibiotics within the past 3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No


Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-13

Curated date: 2021/08/09

Curator: Samara.Khan

Revision editor(s): Samara.Khan

Source: Figure 4 and Discussion section

Description: Patients with stage 3/4 endometriosis had a higher abundance of Anaerococcus than those with stage1/2 endometriosis. Other signatures could not be reported because the rest of the paper grouped OTUs into community state types (CSTs).

Abundance in Group 1: increased abundance in Stage 3/4 Endometriosis patients

NCBI Quality ControlLinks
Anaerococcus

Revision editor(s): Samara.Khan

Experiment 2


Needs review

Curated date: 2023/07/13

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
endometriosis endometriosis,Endometriosis (clinical),endometriosis (disease),Endometriosis (disorder),Endometriosis (morphologic abnormality),ENDOMETRIOSIS NEC,Endometriosis NOS,Endometriosis NOS (disorder),Endometriosis of other specified sites,Endometriosis, site unspecified
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Lower stages of endometriosis
Group 1 name Corresponds to the case (exposed) group for case-control studies
Higher stages of endometriosis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Not specified
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
T-Test
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)?
Yes


Signature 1

Needs review

Curated date: 2023/07/13

Curator: Atrayees

Revision editor(s): Atrayees

Source: Fig 3B

Description: The top contributing OTU features for this model, ranked by Mean Decreased Accuracy.

Abundance in Group 1: decreased abundance in Higher stages of endometriosis

NCBI Quality ControlLinks
Porphyromonas
Neisseria
Haemophilus

Revision editor(s): Atrayees

Signature 2

Needs review

Curated date: 2023/07/13

Curator: Atrayees

Revision editor(s): Atrayees

Source: Fig 3B

Description: The top contributing OTU features for this model, ranked by Mean Decreased Accuracy.

Abundance in Group 1: increased abundance in Higher stages of endometriosis

NCBI Quality ControlLinks
Anaerococcus
Acidovorax
Sphingomonas
Peptoniphilus
Dialister
Phyllobacterium
Howardella
Escherichia
Lactobacillus
Varibaculum
Propionibacterium

Revision editor(s): Atrayees