Correlations between serum cytokines and gut microbiota in patients with Graves’ disease: A case-control study Original paper
-
Autoimmune Diseases
Autoimmune Diseases
Autoimmune disease is when the immune system mistakenly attacks the body's tissues, often linked to imbalances in the microbiome, which can disrupt immune regulation and contribute to disease development.
-
Graves Disease
Graves Disease
OverviewGraves’ Disease (GD) affects approximately 0.5% of the population, predominantly women. First-line treatment options—antithyroid medications, radioactive iodine, and surgery— often result in significant side effects, incomplete remissions, and frequent relapses. Further, current first-line treatment options focus on symptoms management, and reflect an inadequate understanding of the etiology of the condition. However, recent research reveals a […]
-
Giorgos Aristotelous
Giorgos — BSc, MSc. Giorgos is an exercise scientist whose training and professional practice sit at the intersection of human performance, clinical health, and emerging microbiome science. He holds a BSc in Sports Science & Physical Education from Aristotle University (2012) and an MSc in Exercise & Health from Democritus University (2016), where his graduate work explored physiological adaptations to training across the lifespan. Now in his 15th year of practice, Giorgos pairs evidence-based coaching (ACSM-CPT, NSCA, USA Weightlifting) with a research-driven interest in how physical activity, body composition, and musculoskeletal integrity shape—and are shaped by—host–microbiome dynamics.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Giorgos — BSc, MSc. Giorgos is an exercise scientist whose training and professional practice sit at the intersection of human performance, clinical health, and emerging microbiome science. He holds a BSc in Sports Science & Physical Education from Aristotle University (2012) and an MSc in Exercise & Health from Democritus University (2016), where his graduate work explored physiological adaptations to training across the lifespan. Now in his 15th year of practice, Giorgos pairs evidence-based coaching (ACSM-CPT, NSCA, USA Weightlifting) with a research-driven interest in how physical activity, body composition, and musculoskeletal integrity shape—and are shaped by—host–microbiome dynamics.
What was studied?
This case–control observational study investigated the associations between peripheral blood cytokine profiles and gut microbiota composition in patients with Graves’ disease (GD), the most common autoimmune thyroid disorder. The study aimed to elucidate the interplay between immune dysregulation—specifically changes in cytokines such as interleukin-10 (IL-10), transforming growth factor β (TGF-β), and interleukin-17A (IL-17A)—and alterations in gut microbial communities, potentially contributing to GD pathogenesis. These gut microbiome cytokine associations are pivotal to understanding Graves’ disease better. The researchers performed comprehensive profiling using high-resolution 16S rRNA gene sequencing for fecal microbiota and multiplex cytokine arrays for serum immune markers, alongside standard thyroid function testing. The study also included in silico functional prediction of microbial metabolic pathways. Statistical analyses (including alpha and beta diversity, correlation, and discriminant analyses) were employed to identify microbial signatures associated with immune and thyroid dysfunction in GD.
Who was studied?
The study enrolled 30 consecutive, untreated Graves’ disease patients (primarily female, as per GD epidemiology) admitted to the Department of Endocrinology at the Third Affiliated Hospital of Qiqihar Medical University (China) between January and July 2023. Thirty age- and sex-matched healthy controls (HC) were recruited from individuals undergoing routine physical examination in the same period. Exclusion criteria included alternative causes of thyrotoxicosis, autoimmune comorbidities, recent antibiotic/probiotic or immunosuppressive use, pregnancy/lactation, and acute infections, ensuring a focused comparison of GD-specific changes. Both groups were matched for demographic variables, and comprehensive baseline data (age, sex, BMI) were collected.
Most important findings
The study revealed significant gut microbial dysbiosis in Graves’ disease, with lower overall microbial diversity and richness compared to healthy controls. At the phylum level, GD patients exhibited reduced Firmicutes and increased Bacteroidetes. Discriminative analysis identified 19 taxa with altered abundance, most notably: decreased Bifidobacterium and Veillonella (commensals) and increased Prevotella_9 and Megamonas (potential pathobionts). Importantly, cytokine-microbiota correlations showed that anti-inflammatory cytokines (IL-10, TGF-β) were positively associated with Bifidobacterium and Parasutterella, but negatively with Prevotella_9 and Megamonas.
Conversely, the pro-inflammatory cytokine IL-17A was positively correlated with Prevotella_9 and Megamonas and negatively with Bifidobacterium and Veillonella. Key thyroid function indices (TSH, FT3, FT4, TRAb) were also linked to specific bacterial genera, underscoring a multi-layered gut-immune-thyroid axis. Functional predictions indicated upregulation of energy and immune-related pathways in the GD microbiome, alongside downregulation of amino acid metabolism, membrane transport, and xenobiotic degradation.
Key implications
This study provides robust evidence that Graves’ disease is characterized by gut microbial dysbiosis, which is closely intertwined with immune imbalance and thyroid dysfunction. The identification of specific bacterial genera, such as increased Prevotella_9 and Megamonas (linked to pro-inflammatory cytokines and hyperthyroidism), and decreased Bifidobacterium and Veillonella (linked to anti-inflammatory cytokines and thyroid regulation), offers potential microbial biomarkers for GD diagnosis and monitoring. These findings suggest that modulating the gut microbiome or targeting the cytokine-microbiota axis could represent novel therapeutic strategies for GD. Additionally, the study highlights the need for further mechanistic and interventional research to clarify causality and therapeutic potential, as well as validation in larger and more diverse populations.