Gut Microbiome in Graves’ Disease and Orbitopathy: Distinct Signatures and Clinical Implications Original paper
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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.
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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 […]
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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 original research article conducted a comparative assessment of the gut microbial composition and predicted metabolic function in patients with Graves’ disease (GD) and Graves’ orbitopathy (GO), as well as healthy controls. Using 16S rRNA gene sequencing, the authors aimed to identify specific intestinal bacterial taxa and functional signatures associated with GD and GO, in order to better understand the microbiome-related differences between these two clinical phenotypes. The study also explored whether gut microbial features could provide markers to distinguish GO from GD in clinical practice, and how these microbial alterations might relate to disease pathophysiology, particularly autoimmunity.
Who was studied?
The study population consisted of 30 patients with Graves’ disease (GD) without orbitopathy, 33 patients with Graves’ orbitopathy (GO), and 32 healthy control subjects, all recruited from the outpatient department of Beijing Tongren Hospital, Capital Medical University. The three groups were matched for age and sex, and strict inclusion and exclusion criteria were applied, such as age (18-65 years), no recent use of antibiotics, probiotics, hormonal medications, or Chinese herbal medicine, and absence of chronic gastrointestinal disorders, systemic diseases, or other autoimmune conditions. Both GD and GO patients had normalized thyroid hormone levels at the time of sampling, minimizing confounding effects of thyroid dysfunction. GO was diagnosed according to EUGOGO guidelines, and all participants provided informed consent.
Most important findings
The gut microbiota of GD and GO patients showed significant alterations in comparison to healthy controls, with notable differences between the GD and GO groups themselves. Alpha diversity (Shannon index) was significantly reduced in both GD and GO patients relative to controls, indicating lower microbial diversity. At the phylum level, GO patients had a significant decrease in Deinococcus-Thermus and Chloroflexi compared to GD patients. Genus-level analysis revealed that Subdoligranulum and Bilophila were increased, while Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_Lachnospiraceae, unidentified_Clostridiales, Collinsella, Intestinibacter, and Phascolarctobacterium were decreased in GO relative to GD. Additionally, Prevotella copri was enriched in both GD and GO groups compared to controls.
Random forest modeling identified Deinococcus-Thermus, Cyanobacteria, and Chloroflexi as among the top taxa distinguishing between the groups. Importantly, several microbial taxa—including Subdoligranulum and Lachnospiraceae—showed strong associations with serum thyrotropin receptor antibody (TRAb) levels, a key marker of thyroid autoimmunity, even after adjusting for age and sex. Functional predictions (via KEGG pathways) indicated enhanced nucleotide metabolism, energy metabolism, and enzyme family pathways in GD and GO, with viral protein family enrichment specifically in GD.
Key implications
These findings underscore that distinct gut microbiome signatures characterize GD and GO, supporting the hypothesis that gut dysbiosis may contribute to the development and progression of Graves’ orbitopathy in GD patients. The microbial taxa identified—especially the reduction of butyrate-producing and anti-inflammatory bacteria such as Lachnospiraceae and Blautia in GO—suggest mechanisms linking the microbiome to immune activation and orbital inflammation. The robust association of specific microbes with TRAb levels further highlights the potential of gut microbial markers as adjuncts in diagnosis, risk stratification, or even as therapeutic targets for GO. Functional pathway enrichment, notably in nucleotide and energy metabolism, hints at altered host-microbe metabolic interactions in these autoimmune thyroid conditions. However, larger multicenter studies and mechanistic investigations are needed to confirm causality and clinical utility.