Alteration in gut microbiota is associated with immune imbalance in Graves' disease

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

38533382

DOI Digital object identifier for electronic documents.

https://doi.org/10.3389/fcimb.2024.1349397

URI Uniform resource identifier for web resources.

Authors

Liu Y, Tang S, Feng Y, Xue B, Cheng C, Su Y, Wei W, Zhang L, Huang Z, Shi X, Fang Y, Yang J, Zhang Y, Deng X, Wang L, Ren H, Wang C, Yuan H

Journal

Frontiers in cellular and infection microbiology

Year

2024

Keywords:

B cells, Graves’ disease, LPS, cytokines, gut microbiota

BACKGROUND: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. OBJECTIVE: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. METHODS: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. RESULTS: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. CONCLUSION: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.

Experiment 1

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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 Controls (HCs)

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

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: 33

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: 3.0

Alpha Diversity

Pielou Quantifies how equal the community is numerically: unchanged

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

Richness Number of species: unchanged

Signature 1

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Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 2C

Description: Linear discriminant analysis (LEfSe, LDA>3) showing alternation of gut microbiota compared with HCs.

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

NCBI	Quality Control	Links
Ruminococcus gauvreauii
Weissella
Collinsella
Enterococcus
Streptococcus
Blautia
Lactobacillus
Bifidobacterium

Revision editor(s): Aleru Divine

Signature 2

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 2C

Description: Linear discriminant analysis (LEfSe, LDA>3) showing alternation of gut microbiota compared with HCs.

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

NCBI	Quality Control	Links
Bacteroides
Dialister
Alistipes
Ruminococcaceae bacterium UCG-002Ruminococcaceae bacterium UCG-002
Christensenellaceae R-7 groupChristensenellaceae R-7 group
Fusicatenibacter
rumen bacterium NK4A214
Parabacteroides

Revision editor(s): Aleru Divine