Oral, Vaginal, and Stool Microbial Signatures in Patients With Endometriosis as Potential Diagnostic Non-Invasive Biomarkers: A Prospective Cohort Study

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Hicks C, Leonardi M, Chua XY, Mari-Breedt L, Espanda M, El-Omar EM, Condous G, El-Assaad F
Journal
BJOG : an international journal of obstetrics and gynaecology
Year
2024
Keywords:
bacteria, biomarker, diagnostic, dysbiosis, endometriosis, inflammation, microbiome, microbiota, oral
OBJECTIVE: To identify a microbial signature for endometriosis for use as a diagnostic non-invasive biomarker. DESIGN: Prospective cohort pilot study. SETTING: Nepean Hospital and UNSW Microbiome Research Centre, Australia. POPULATION: Sixty-four age- and sex-matched subjects (n = 19 healthy control (HC); n = 24 non-endometriosis (N-ENDO) and n = 21 confirmed endometriosis (ENDO)). All study participants, besides healthy controls, underwent laparoscopic surgical assessment for endometriosis, and histology was performed on excised lesions. METHODS: Oral, stool and, vaginal samples were self-collected at a single time point for healthy controls, and preoperatively for patients undergoing laparoscopy. Samples underwent 16S rRNA amplicon sequencing, followed by bioinformatics analysis. MAIN OUTCOME MEASURES: Compositional differences between cohorts as identified by diversity analyses, and differentially abundant microbial taxa, as identified by LEfSE analysis. RESULTS: The composition of the oral (adjusted p = 0.003), and stool (adjusted p = 0.042) microbiota is different between the three cohorts. Differentially abundant taxa are present within each cohort as identified by LEfSE analysis. Particularly, Fusobacterium was enriched in the oral samples of patients with moderate/severe endometriosis. CONCLUSIONS: Taxonomic and compositional differences were found between the microbiota in the mouth, gut and, vagina of patients with and without endometriosis and healthy controls. Fusobacterium was enriched in patients with moderate/severe endometriosis. Fusobacterium is noted as a key pathogen in periodontal disease, a common comorbidity in endometriosis. These findings suggest a role for the oral, stool and, vaginal microbiome in endometriosis, and present potential for microbial-based treatments and the design of a diagnostic swab.

Experiment 1


Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Subjects

Location of subjects
Australia
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
Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth,mouth
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
Endometriosis and Non-endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Healthy control cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the healthy control cohort were women with no known gynaecological symptoms or infertility concerns.
Group 0 sample size Number of subjects in the control (unexposed) group
45
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-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).
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
2.0
Matched on Factors on which subjects have been matched on in a case-control study
age, sex


Signature 1

Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis

Abundance in Group 1: increased abundance in Healthy control cohort

NCBI Quality ControlLinks
Actinobacillus
Butyrivibrio
Lactococcus
Lautropia
Neisseria
Neisseriaceae
Peptostreptococcaceae
Prevotella

Revision editor(s): Aleru Divine

Experiment 2


Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control and Non-endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Endometriosis cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the endometriosis cohort were women who were confirmed to have endometriosis.
Group 0 sample size Number of subjects in the control (unexposed) group
43
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis

Abundance in Group 1: increased abundance in Endometriosis cohort

NCBI Quality ControlLinks
Veillonella
bacterium F16
Actinomycetaceae

Revision editor(s): Aleru Divine

Experiment 3


Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control and endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-endometriosis cohorts
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the non-endometriosis cohort were women who had confirmed gynaecological pathologies such as fibroids, abnormal uterine bleeding and ovarian cysts.
Group 0 sample size Number of subjects in the control (unexposed) group
40
Group 1 sample size Number of subjects in the case (exposed) group
24

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis

Abundance in Group 1: increased abundance in Non-endometriosis cohorts

NCBI Quality ControlLinks
Megasphaera
Bifidobacterium
Lactobacillus

Revision editor(s): Aleru Divine

Experiment 4


Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Endometriosis and Non-endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Healthy control cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the healthy control cohort were women with no known gynaecological symptoms or infertility concerns.
Group 0 sample size Number of subjects in the control (unexposed) group
45
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis

Abundance in Group 1: increased abundance in Healthy control cohort

NCBI Quality ControlLinks
Eubacteriales
Lachnospira
Butyricicoccus
Victivallaceae
Peptococcaceae
Bacteria
RF39RF39
RF32RF32

Revision editor(s): Aleru Divine

Experiment 5


Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control and Non-endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Endometriosis cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the endometriosis cohort were women who were confirmed to have endometriosis.
Group 0 sample size Number of subjects in the control (unexposed) group
43
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis

Abundance in Group 1: increased abundance in Endometriosis cohort

NCBI Quality ControlLinks
Phascolarctobacterium
Lactobacillus
Haemophilus

Revision editor(s): Aleru Divine

Experiment 6


Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control and endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-endometriosis cohorts
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the non-endometriosis cohort were women who had confirmed gynaecological pathologies such as fibroids, abnormal uterine bleeding and ovarian cysts.
Group 0 sample size Number of subjects in the control (unexposed) group
40
Group 1 sample size Number of subjects in the case (exposed) group
24

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/08

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis

Abundance in Group 1: increased abundance in Non-endometriosis cohorts

NCBI Quality ControlLinks
Eubacterium
Bacteroidales

Revision editor(s): Aleru Divine

Experiment 7


Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Vagina Vagina,vagina,Distal oviductal region,Distal portion of oviduct,Vaginae
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Endometriosis and Non-endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Healthy control cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the healthy control cohort were women with no known gynaecological symptoms or infertility concerns.
Group 0 sample size Number of subjects in the control (unexposed) group
45
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis.

Abundance in Group 1: increased abundance in Healthy control cohort

NCBI Quality ControlLinks
Salmonella
Listeria
Pseudomonas
Bacillus

Revision editor(s): MyleeeA

Experiment 8


Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control and Non-endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Endometriosis cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the endometriosis cohort were women who were confirmed to have endometriosis.
Group 0 sample size Number of subjects in the control (unexposed) group
43
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis.

Abundance in Group 1: increased abundance in Endometriosis cohort

NCBI Quality ControlLinks
Escherichia
Enterococcus
Tepidimonas
Thermus

Revision editor(s): MyleeeA

Experiment 9


Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy control and endometriosis cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-endometriosis cohorts
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants in the non-endometriosis cohort were women who had confirmed gynaecological pathologies such as fibroids, abnormal uterine bleeding and ovarian cysts.
Group 0 sample size Number of subjects in the control (unexposed) group
40
Group 1 sample size Number of subjects in the case (exposed) group
24

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 5

Description: Microbial features that were detected to be differentially abundant between the three cohorts using LEfSe analysis.

Abundance in Group 1: increased abundance in Non-endometriosis cohorts

NCBI Quality ControlLinks
Sneathia
Haemophilus
Prevotella
Weeksellaceae

Revision editor(s): MyleeeA

Experiment 10


Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Mouth Adult mouth,Cavital oralis,Cavitas oris,Cavum oris,Mouth cavity,Oral region,Oral vestibule,Regio oralis,Rima oris,Stoma,Stomatodaeum,Trophic apparatus,Vestibule of mouth,Vestibulum oris,Mouth,mouth
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Minimal/Mild endometriosis
Group 1 name Corresponds to the case (exposed) group for case-control studies
Moderate/Severe endometriosis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients who underwent laparoscopy with confirmed endometriosis (ENDO) Stages 3 and 4 further grouped as Moderate/Severe endometriosis.
Group 0 sample size Number of subjects in the control (unexposed) group
12
Group 1 sample size Number of subjects in the case (exposed) group
9

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 6

Description: Microbial features that were detected to be differentially abundant using LEfSe analysis between patients with Minimal/Mild stage endometriosis and patients with Moderate/Severe endometriosis in oral samples.

Abundance in Group 1: increased abundance in Moderate/Severe endometriosis

NCBI Quality ControlLinks
Fusobacterium

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 6

Description: Microbial features that were detected to be differentially abundant using LEfSe analysis between patients with Minimal/Mild stage endometriosis and patients with Moderate/Severe endometriosis in oral samples.

Abundance in Group 1: decreased abundance in Moderate/Severe endometriosis

NCBI Quality ControlLinks
Cardiobacterium

Revision editor(s): MyleeeA

Experiment 11


Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces


Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 6

Description: Microbial features that were detected to be differentially abundant using LEfSe analysis between patients with Minimal/Mild stage endometriosis and patients with Moderate/Severe endometriosis in stool samples.

Abundance in Group 1: increased abundance in Moderate/Severe endometriosis

NCBI Quality ControlLinks
unclassified Paraprevotella

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 6

Description: Microbial features that were detected to be differentially abundant using LEfSe analysis between patients with Minimal/Mild stage endometriosis and patients with Moderate/Severe endometriosis in stool samples.

Abundance in Group 1: decreased abundance in Moderate/Severe endometriosis

NCBI Quality ControlLinks
Actinomyces

Revision editor(s): MyleeeA

Experiment 12


Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Vagina Vagina,vagina,Distal oviductal region,Distal portion of oviduct,Vaginae


Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/12

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 6

Description: Microbial features that were detected to be differentially abundant using LEfSe analysis between patients with Minimal/Mild stage endometriosis and patients with Moderate/Severe endometriosis in vaginal samples.

Abundance in Group 1: increased abundance in Moderate/Severe endometriosis

NCBI Quality ControlLinks
Blautia
Dorea
Collinsella
Eubacterium

Revision editor(s): MyleeeA