Gut microbiome in endometriosis: a cohort study on 1000 individuals
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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 Uniform resource identifier for web resources.
Authors
Pérez-Prieto I, Vargas E, Salas-Espejo E, Lüll K, Canha-Gouveia A, Pérez LA, Fontes J, Salumets A, Andreson R, Aasmets O, Whiteson K, Org E, Altmäe S
Journal
BMC medicine
Year
2024
Keywords:
Endometriosis, Estrobolome, Gut microbiota, Metagenomics, Microbiome, Microbiota, Shotgun sequencing
BACKGROUND: Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case-control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. METHODS: A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes' sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. RESULTS: Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R 2 < 0.0007, p-values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes' sequence reads were not significantly different between groups (all FDR p-values > 0.05). CONCLUSIONS: Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.
Experiment 1
Reviewed Marked as Reviewed by KateRasheed on 2025-5-7
Subjects
- Location of subjects
- Estonia
- 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
- 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
- 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
- Control
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Endometriosis Cases
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Study participants diagnosed with endometriosis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 864
- Group 1 sample size Number of subjects in the case (exposed) group
- 136
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).
- log transformation
- Statistical test
- ANCOM-BC
- 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
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, proton-pump inhibitor, Confounders controlled for: "antibiotic consumption" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.antibiotic consumption, Confounders controlled for: "stool consistency" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.stool consistency, Confounders controlled for: "anti-inflammatory drug" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.anti-inflammatory drug, Confounders controlled for: "constipation drug" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.constipation drug, Confounders controlled for: "gut emptying frequency" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gut emptying frequency
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-5-7
Source: Additional file 2: Table S2
Description: Significant differential abundant taxa in endometriosis and control groups
Abundance in Group 1: increased abundance in Endometriosis Cases
Revision editor(s): Montana-D
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-5-7
Source: Additional file 2: Table S2
Description: Significant differential abundant taxa in endometriosis and control groups
Abundance in Group 1: decreased abundance in Endometriosis Cases
Revision editor(s): Montana-D
Experiment 2
Reviewed Marked as Reviewed by KateRasheed on 2025-5-7
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Women with endometriosis at their reproductive age (≤ 50 years)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 525
- Group 1 sample size Number of subjects in the case (exposed) group
- 66
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, proton-pump inhibitor, Confounders controlled for: "antibiotic consumption" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.antibiotic consumption, Confounders controlled for: "anti-inflammatory drug" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.anti-inflammatory drug, Confounders controlled for: "constipation drug" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.constipation drug, Confounders controlled for: "gut emptying frequency" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gut emptying frequency, Confounders controlled for: "stool consistency" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.stool consistency
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-5-7
Source: Additional File 2: Supplementary Table 5
Description: Sensitivity differential abundance analysis in endometriosis and control groups. Species with a prevalence >10% and relative abundance ≥0.1% were compared in endometriosis and control groups after excluding women with age >50, using an Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC).
Abundance in Group 1: increased abundance in Endometriosis Cases
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-5-7
Source: Additional File 2: Supplementary Table 5
Description: Sensitivity differential abundance analysis in endometriosis and control groups. Species with a prevalence >10% and relative abundance ≥0.1% were compared in endometriosis and control groups after excluding women with age >50, using an Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC).
Abundance in Group 1: decreased abundance in Endometriosis Cases
Revision editor(s): MyleeeA
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