Endometriosis induces gut microbiota alterations in mice

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Reviewed Marked as Reviewed by Fatima on 2022/03/14
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yuan M, Li D, Zhang Z, Sun H, An M, Wang G
Journal
Human reproduction (Oxford, England)
Year
2018
STUDY QUESTION: What happens to the gut microbiota during development of murine endometriosis? SUMMARY ANSWER: Mice with the persistence of endometrial lesions for 42 days develop a distinct composition of gut microbiota. WHAT IS KNOWN ALREADY: Disorders in the immune system play fundamental roles in changing the intestinal microbiota. No study has used high-throughput DNA sequencing to show how endometriosis changes the gut microbiota, although endometriosis is accompanied by abnormal cytokine expression and immune cell dysfunction. STUDY DESIGN, SIZE, DURATION: This study includes a prospective and randomized experiment on an animal endometriosis model induced via the intraperitoneal injection of endometrial tissues. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mice were divided into endometriosis and mock groups and were sacrificed at four different time points for model confirmation and fecal sample collection. To detect gut microbiota, 16S ribosomal-RNA gene sequencing was performed. Alpha diversity was used to analyze the complexity and species diversity of the samples through six indices. Beta diversity analysis was utilized to evaluate the differences in species complexity. Principal coordinate analysis and unweighted pair-group method with arithmetic means clustering were performed to determine the clustering features. The microbial features differentiating the fecal microbiota were characterized by linear discriminant analysis effect size method. MAIN RESULTS AND THE ROLE OF CHANCE: The endometriosis and mock mice shared similar diversity and richness of gut microbiota. However, different compositions of gut microbiota were detected 42 days after the modeling. Among the discriminative concrete features, the Firmicutes/Bacteroidetes ratio was elevated in mice with endometriosis, indicating that endometriosis may induce dysbiosis. Bifidobacterium, which is known as a commonly used probiotic, was also increased in mice with endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: More control groups should be further studied to clarify the specificity of the dysbiosis induced by endometriosis. This study was performed only on mice. Thus, additional data acquired from patients with endometriosis are needed in future research. We only detected the changes of gut microbiota at 42 days after the modeling, while the long-term effect of endometriosis on gut microbiota remains poorly understood. Moreover, we only revealed a single effect of endometriosis on gut microbiota. WIDER IMPLICATIONS OF THE FINDINGS: This study provided the first comprehensive data on the association of endometriosis and gut microbiota from high-throughput sequencing technology. The gut microbiota changed with the development of endometriosis in a murine model. The communication between the host and the gut microbiota is bidirectional, and further studies should be performed to clarify their relationship. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Grant (81571417) from the National Science Foundation of China and Grant (2015GSF118092) from the Technology Development Plan of Shandong Province. The authors report no conflict of interest.

Experiment 1


Reviewed Marked as Reviewed by Fatima on 2022/03/14

Curated date: 2021/08/08

Curator: Samara.Khan

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

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
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
Healthy mice
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice who were injected with endometrial tissues
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Researchers induced endometriosis models by intraperitoneal injection of endometrial tissues to mimic endometriosis formation in humans.
Group 0 sample size Number of subjects in the control (unexposed) group
4
Group 1 sample size Number of subjects in the case (exposed) group
4
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
N/A

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/03/14

Curated date: 2021/08/08

Curator: Samara.Khan

Revision editor(s): Fatima, Samara.Khan

Source: Figure 4

Description: Researchers used t-tests to calculate the differences in microbiota at the taxon level between the control and experimental groups.

The following bacterial taxa were more abundant in mice with simulated endometriosis than in mice without endometriosis.

Abundance in Group 1: increased abundance in Mice who were injected with endometrial tissues

NCBI Quality ControlLinks
Actinomycetota
Alcaligenaceae
Betaproteobacteria
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Burkholderiales
Bacillota
Parasutterella

Revision editor(s): Fatima, Samara.Khan

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/03/14

Curated date: 2021/08/08

Curator: Samara.Khan

Revision editor(s): Samara.Khan

Source: Figure 4

Description: Researchers used the LEfse method to determine the predominant microbiota in each sample. They then used t-tests to calculate the differences in microbiota at the taxon level between the control and experimental groups.

The following bacterial taxa were less abundant in mice with simulated endometriosis than in mice without endometriosis.

Abundance in Group 1: decreased abundance in Mice who were injected with endometrial tissues

NCBI Quality ControlLinks
Bacteroidota
Bacteroidia
Bacteroidales

Revision editor(s): Samara.Khan

Experiment 2


Reviewed Marked as Reviewed by Chloe on 2023-3-9

Curated date: 2022/03/14

Curator: Fatima

Revision editor(s): WikiWorks, Fatima, Chloe

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

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Chloe on 2023-3-9

Curated date: 2022/03/14

Curator: Fatima

Revision editor(s): WikiWorks, Fatima

Source: Figure 4

Description: LDA coupled with effect size measurements identified the most differentially abundant taxa between the two groups

Abundance in Group 1: increased abundance in Mice who were injected with endometrial tissues

NCBI Quality ControlLinks
Bacillota

Revision editor(s): WikiWorks, Fatima

Signature 2

Reviewed Marked as Reviewed by Chloe on 2023-3-9

Curated date: 2022/03/14

Curator: Fatima

Revision editor(s): WikiWorks, Fatima

Source: Figure 4

Description: LDA coupled with effect size measurements identified the most differentially abundant taxa between the two groups

Abundance in Group 1: decreased abundance in Mice who were injected with endometrial tissues

NCBI Quality ControlLinks
Alloprevotella
Bacteroidia
Bacteroidales
Bacteroidota

Revision editor(s): WikiWorks, Fatima