Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Shi TT, Xin Z, Hua L, Wang H, Zhao RX, Yang YL, Xie RR, Liu HY, Yang JK
Journal
Journal of endocrinological investigation
Year
2021
Keywords:
16S rRNA gene, Graves’ disease, Graves’ orbitopathy, Gut microbiota, Metabolic functions
BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

Experiment 1


Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

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
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
Graves disease Basedow disease,Basedow's disease,exophthalmic goiter,Flajani-Basedow-Graves disease,grave's disease,Graves disease,Graves' disease,Graves' hyperthyroidism,parry disease,toxic diffuse goiter,graves disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy subjects
Group 1 name Corresponds to the case (exposed) group for case-control studies
Graves’ disease (GD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with Graves’ disease (GD)
Group 0 sample size Number of subjects in the control (unexposed) group
32
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
One month

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
Ion Torrent

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased

Signature 1

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5B and 6B

Description: Comparison of the changes in the structure of the fecal microbiota profile

Abundance in Group 1: increased abundance in Graves’ disease (GD)

NCBI Quality ControlLinks
Deinococcota
Chloroflexota
unclassified Erysipelotrichaceae
Romboutsia
Dorea
unclassified Lachnospiraceae
Intestinibacter
Blautia
unclassified Prevotellaceae

Revision editor(s): Aleru Divine

Signature 2

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5B and 6B

Description: Comparison of the changes in the structure of the fecal microbiota profile

Abundance in Group 1: decreased abundance in Graves’ disease (GD)

NCBI Quality ControlLinks
Subdoligranulum
Bilophila
Alistipes
Odoribacter
Bacteroides

Revision editor(s): Aleru Divine

Experiment 2


Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Graves ophthalmopathy Congestive Ophthalmopathy,Dysthyroid Ophthalmopathy,dysthyroid/thyroid-associated orbitopathy (TAO),Edematous Ophthalmopathy,Graves' ophthalmopathy,Graves' orbitopathy,Myopathic Ophthalmopathy,thyroid eye disease (TED),Thyroid-Associated Ophthalmopathies,Thyroid-Associated Ophthalmopathy,Graves ophthalmopathy,graves ophthalmopathy
Group 1 name Corresponds to the case (exposed) group for case-control studies
Graves’ ophthalmopathy (GO)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with Graves’ ophthalmopathy (GO)
Group 1 sample size Number of subjects in the case (exposed) group
33

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased

Signature 1

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure A and 6A

Description: Comparison of the changes in the structure of the fecal microbiota profile.

Abundance in Group 1: increased abundance in Graves’ ophthalmopathy (GO)

NCBI Quality ControlLinks
Bacteroidota
unclassified Prevotellaceae

Revision editor(s): Aleru Divine

Signature 2

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure A and 6A

Description: Comparison of the changes in the structure of the fecal microbiota profile.

Abundance in Group 1: decreased abundance in Graves’ ophthalmopathy (GO)

NCBI Quality ControlLinks
Bacillota
Anaerostipes
Blautia
Fusicatenibacter
Butyricicoccus
Collinsella

Revision editor(s): Aleru Divine

Experiment 3


Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Graves disease , Graves ophthalmopathy Basedow disease,Basedow's disease,exophthalmic goiter,Flajani-Basedow-Graves disease,grave's disease,Graves disease,Graves' disease,Graves' hyperthyroidism,parry disease,toxic diffuse goiter,graves disease,Congestive Ophthalmopathy,Dysthyroid Ophthalmopathy,dysthyroid/thyroid-associated orbitopathy (TAO),Edematous Ophthalmopathy,Graves' ophthalmopathy,Graves' orbitopathy,Myopathic Ophthalmopathy,thyroid eye disease (TED),Thyroid-Associated Ophthalmopathies,Thyroid-Associated Ophthalmopathy,Graves ophthalmopathy,graves ophthalmopathy
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Graves’ ophthalmopathy (GO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Graves’ disease (GD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with Graves’ disease (GD)
Group 0 sample size Number of subjects in the control (unexposed) group
33
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5C and 6C

Description: Comparison of the changes in the structure of the fecal microbiota profile.

Abundance in Group 1: increased abundance in Graves’ disease (GD)

NCBI Quality ControlLinks
Deinococcota
Chloroflexota
Blautia
Anaerostipes
Dorea
Butyricicoccus
Romboutsia
Fusicatenibacter
unclassified Lachnospiraceae
unclassified Eubacteriales
Collinsella
Intestinibacter
Phascolarctobacterium

Revision editor(s): Aleru Divine

Signature 2

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 5C and 6C

Description: Comparison of the changes in the structure of the fecal microbiota profile

Abundance in Group 1: decreased abundance in Graves’ disease (GD)

NCBI Quality ControlLinks
Subdoligranulum
Bilophila

Revision editor(s): Aleru Divine