Graves’ Disease Gut Microbiome Signatures: Key Genera and Clinical Implications Original paper

What was studied?

This prospective study investigated the relationship between gut microbiota composition and the development of Graves’ disease (GD), with a particular focus on identifying distinct microbial signatures and their associations with immune dysregulation. Using 16S rRNA sequencing, the researchers profiled the gut microbiota in newly diagnosed GD patients both before and after antithyroid drug (ATD) therapy, compared to healthy controls. The study aimed to characterize alterations in gut microbial diversity and specific taxa, evaluate their associations with clinical and immune parameters (including cytokines such as IL-17), and assess the impact of standard GD treatment on restoring microbiome balance. Importantly, the study utilized machine learning (random forest analysis) to identify bacterial genera that could distinguish GD patients from healthy individuals with high accuracy, offering potential for diagnostic biomarker development and deeper insight into the gut-immune-thyroid axis.

Who was studied?

The study enrolled 65 newly diagnosed, untreated Graves’ disease patients (18 men, 47 women; median age 30) of Chinese Han ethnicity, treated at the Endocrinology Department of the First Affiliated Hospital of Nanchang University between October 2018 and September 2019. Thirty-seven of these patients completed a 3-month follow-up after receiving methimazole-based ATD therapy. The control group comprised 33 healthy volunteers (10 men, 23 women; median age 27) with no known diseases. All participants provided fecal and blood samples for microbiome and clinical parameter analyses. Strict inclusion and exclusion criteria were applied to avoid confounding factors such as recent antibiotic, probiotic, or prebiotic use, and comorbid autoimmune, gastrointestinal, hepatic, or endocrine diseases. The study also performed a subgroup analysis of GD patients with and without impaired liver function.

Most important findings

The gut microbiota of GD patients exhibited significantly lower richness and diversity compared to healthy controls, indicating marked dysbiosis. At baseline, notable microbial shifts included increased abundance of Bacilli (class), Lactobacillales (order), Streptococcaceae (family), and the genera Streptococcus, Veillonella, and Erysipelatoclostridium, all associated with pro-inflammatory states. In contrast, key short-chain fatty acid (SCFA)-producing and anti-inflammatory taxa—such as Peptostreptococcaceae, Christensenellaceae, Marinifilaceae, Rikenellaceae (families), and Roseburia, Romboutsia, Lachnospira, Eubacterium ventriosum (genera)—were significantly decreased in GD patients. After 3 months of ATD therapy, the microbiota composition of GD patients began to recover toward that of healthy controls, with partial restoration of SCFA-producing taxa and reduction of pro-inflammatory genera. IL-17, a cytokine associated with Th17-mediated immune response, decreased significantly post-treatment, and its levels correlated inversely with SCFA-producing bacteria such as Eubacterium hallii. Random forest analysis identified 12 bacterial genera—including Veillonella, Streptococcus, and Roseburia—that could collectively distinguish GD patients from controls with high diagnostic accuracy (AUC=0.90). Subgroup analysis revealed that reductions in Weissella and Leuconostocaceae were linked to impaired liver function in GD. Overall, the findings support a model where GD is associated with gut dysbiosis characterized by loss of beneficial, anti-inflammatory taxa and enrichment of pro-inflammatory bacteria, contributing to immune imbalance and disease pathogenesis.

Key implications

The study demonstrates that specific gut microbiome signatures are closely associated with Graves’ disease, highlighting dysbiosis as a potential contributor to immune dysregulation and disease progression. The partial recovery of microbiome composition and immune markers following antithyroid therapy suggests that gut microbiota may be both a biomarker and a therapeutic target in GD. The identification of 12 key bacterial genera that robustly differentiate GD from healthy states provides a foundation for future diagnostic tools, potentially enabling earlier detection or risk stratification. Moreover, associations between specific taxa and immune/inflammatory parameters (e.g., Th17/Treg balance, IL-17) lend support to the concept of microbiota-mediated modulation of autoimmune thyroid disease. These findings encourage further exploration of microbiome-targeted interventions—such as probiotics, prebiotics, or fecal microbiota transplantation—to restore microbial balance and improve clinical outcomes in GD. The study also underscores the need for longer-term and larger-scale research to validate and expand upon these results.