The role of the vaginal microbiome in distinguishing female chronic pelvic pain caused by endometriosis/adenomyosis

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Reviewed Marked as Reviewed by Atrayees on 2023-7-17
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Chao X, Liu Y, Fan Q, Shi H, Wang S, Lang J
Journal
Annals of translational medicine
Year
2021
Keywords:
16S rRNA, Chronic pelvic pain (CPP), endometriosis/adenomyosis (EM/AM), function prediction, vaginal microbiome
Background: This study aimed to investigate the specific vaginal microbiome in the differential diagnosis of endometriosis/adenomyosis (EM/AM)-associated chronic pelvic pain (CPP) from other types of CPP, and to explore the role of the vaginal microbiome in the mechanism of EM/AM-associated CPP. Methods: We recruited 37 women with EM/AM-associated CPP, 25 women with chronic pelvic pain syndrome (CPPS) without EM/AM, and 66 women without CPPS into our study. All of the participants were free from human papillomavirus (HPV) infection. Sequencing of barcoded 16S rRNA gene fragments (V4) was used to determine the vaginal microbiome composition on the Illumina HiSeq2500 System. Taxonomic and functional bioinformatics analyses were performed using t-test, linear discriminant analysis effect size (LEfSe), MetaStat, and PICRUSt algorithms. Results: At the species level, EM/AM-associated CPP was found to be associated with a predominance of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis, and a concomitant paucity of Lactobacillus jensenii, Lactobacillus reuteri, and Lactobacillus iners. When the relative abundance of Clostridium disporicum was over 0.001105% and that of Lactobacillus reuteri was under 0.1911349%, the differential diagnostic sensitivity and specificity were 81.08% and 52.0%, respectively. When serum CA125 was combined, the sensitivity increased to 89.19%, but the specificity remained at 52.0%. The PICRUSt results identified 7 differentially regulated pathways within the 3 groups that may be of relevance. Conclusions: Compared to that of CPPS patients without EM/AM and women without CPPS, the vaginal microbiome of patients with EM/AM-associated CPP shows significantly higher alpha (phylogenetic) diversity, as well as higher counts of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis. These differences in the vaginal microbiome may interfere with local functional pathways, which could provide a direction for innovative metabolite-specific targeted treatment. The combination of vaginal biomarkers and serum CA125 may provide an original method to differentiate EM/AM-associated CPP.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2021/08/11

Curator: Samara.Khan

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

Subjects

Location of subjects
China
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 Pars posterior fornicis vaginae,Posterior fornix,Posterior part of fornix of vagina,Posterior fornix of vagina,posterior fornix of 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,Endometriosis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Women without CPPS presenting for routine examinations
Group 1 name Corresponds to the case (exposed) group for case-control studies
Women with EM-associated CPPS
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Thirty-seven women with endometriosis-associated chronic pelvic pain syndrome (CPPS) confirmed by exploratory laparoscopy or surgical pathology
Group 0 sample size Number of subjects in the control (unexposed) group
66
Group 1 sample size Number of subjects in the case (exposed) group
37
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Patients were excluded if they had taken antibiotics within 14 days prior to sampling

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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
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)?
No
Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2021/08/11

Curator: Samara.Khan

Revision editor(s): Samara.Khan, Atrayees

Source: Table 2

Description: The following taxa were found to be decreased in women with endometriosis associated CPPS.

Abundance in Group 1: decreased abundance in Women with EM-associated CPPS

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): Samara.Khan, Atrayees

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2021/08/11

Curator: Samara.Khan

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

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).
relative abundances
Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4

Alpha Diversity

Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2021/08/11

Curator: Samara.Khan

Revision editor(s): Samara.Khan, Atrayees

Source: Table 2

Description: The following taxa were increased in women with endometriosis associated CPPS pain

Abundance in Group 1: increased abundance in Women with EM-associated CPPS

NCBI Quality ControlLinks
Alloscardovia
Stenotrophomonas
Veillonella

Revision editor(s): Samara.Khan, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2021/08/11

Curator: Samara.Khan

Revision editor(s): Samara.Khan, Atrayees

Source: Table 2

Description: The following taxa were decreased in women with endometriosis associated CPPS pain

Abundance in Group 1: decreased abundance in Women with EM-associated CPPS

NCBI Quality ControlLinks
Megasphaera
Shuttleworthella
Sneathia

Revision editor(s): Samara.Khan, Atrayees

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2023/07/17

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,Endometriosis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Thirty-seven women with endometriosis-associated chronic pelvic pain syndrome (CPPS) confirmed by exploratory laparoscopy or surgical pathology

Lab analysis

Statistical Analysis

Statistical test
Metastats
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
Not specified
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-17

Curated date: 2023/07/17

Curator: Atrayees

Revision editor(s): Atrayees

Source: Table 2

Description: The following taxa were increased in women with endometriosis associated CPPS pain

Abundance in Group 1: increased abundance in Women with EM-associated CPPS

NCBI Quality ControlLinks
Alloscardovia

Revision editor(s): Atrayees