Correlations between serum cytokines and gut microbiota in patients with Graves' disease: A case-control study

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

40550033

DOI Digital object identifier for electronic documents.

http://doi.org/10.1097/MD.0000000000043000

URI Uniform resource identifier for web resources.

Authors

Chao H, Shan J, Che LQ, Cheng Y, Li HJ, Qian XY

Journal

Medicine

Year

2025

Keywords:

16S rRNA, Graves’ disease, correlation analysis, cytokines, gut microbiota

Graves' disease (GD) is the most prevalent autoimmune thyroid disorder. Gut microbiome as a critical modulator of autoimmune pathogenesis through its bidirectional communication with host immunity. To elucidate the pathophysiological interplay between cellular immunity and gut microbiome composition in GD through systematic analysis of associations between peripheral blood cytokine profiles and microbial community dynamics. This case-control study enrolled 30 untreated GD patients consecutively admitted to the Department of Endocrinology at the Third Affiliated Hospital of Qiqihar Medical University between January and July 2023, along with 30 age/sex-matched healthy controls (HC). Comprehensive evaluations included: electrochemiluminescence immunoassay quantification of thyroid function parameters, high-resolution Illumina HiSeq 2000 platform-based 16S rRNA gene sequencing for fecal microbial community profiling, multiplex cytokine array analysis of peripheral blood immune markers. Spearman correlation analyses were conducted to delineate relationships among cytokines, thyroid function index and gut microbial taxa alterations in GD pathogenesis. Alpha diversity analysis revealed that the abundance and diversity of certain microbiota in the GD group decreased. Beta diversity analysis revealed that the intestinal microbiome composition of GD patients was significantly different from that of HC. The proportion of Firmicutes in patients with GD was lower than that in HC, while the proportion of Bacteroidetes in patients with GD was greater than that in HC. Immunoregulatory cytokine interleukin-10 exhibited positive correlations with commensal genera Bifidobacterium (R = 0.28) and Parasutterella (R = 0.30), while showing negative correlations with the pathobionts Prevotella_9 (r = -0.51) and Megamonas (r = -0.31). Transforming growth factor β demonstrated similar positive correlations with Bifidobacterium (R = 0.31) and negative correlations with Prevotella_9 (r = -0.45) and Megamonas (r = -0.38). Interleukin-17A displayed positive correlated with Prevotella_9 (R = 0.43) and Megamonas (R = 0.32), but negative correlations with Bifidobacterium (r = -0.27), Veillonella (r = -0.47), Prevotella_9 (r = -0.51) and Megamonas (r = -0.31). Clinically, key microbial taxa showed significant associations with thyroid dysfunction parameters. Our findings identify that GD gut ecosystem demonstrates profound microbial dysbiosis characterized by depleted commensal symbionts and expansion of immunomodulatory pathobionts. Specific bacterial taxa correlate with both cytokine and clinical thyroid dysfunction markers.

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 Control (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: The participants in this group were untreated Graves’ disease (GD) patients.

Group 0 sample size Number of subjects in the control (unexposed) group: 30

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: 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: 4.0

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

Alpha Diversity

Pielou Quantifies how equal the community is numerically: increased

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

Chao1 Abundance-based estimator of species richness: increased

Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Richness Number of species: increased

Signature 1

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Curated date: 2025/07/24

Curator: Aleru Divine

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Source: Figure 2

Description: Statistical analysis of the difference in the gut microbiota between the Graves’ disease patients and the healthy controls.

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

NCBI	Quality Control	Links
Bacteroidales
Bacteroidota
Bacteroidia
Prevotella
Prevotellaceae
Phocaeicola plebeius

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 2

Description: Statistical analysis of the difference in the gut microbiota between the Graves’ disease patients and the healthy controls.

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

NCBI	Quality Control	Links
Selenomonadaceae
Megamonas
Subdoligranulum
Klebsiella
Veillonella
Bacteroides fragilis
Shigella
Veillonellaceae
Enterobacterales
Enterobacteriaceae
Gammaproteobacteria
Pseudomonadota
Bacillota

Revision editor(s): Aleru Divine