Graves’ Disease Gut Microbiome Signature: Diagnostic and Pathogenic Insights Original paper

What was studied?

This cross-sectional original research article investigated the composition and metabolic functions of the gut microbiota in patients with Graves’ disease (GD) compared to healthy controls. Using high-throughput 16S rRNA gene sequencing of fecal samples, the study aimed to profile differences in microbial diversity, identify specific taxonomic shifts, and examine associations between gut microbiota and thyroid function, autoimmunity, and metabolism. The research further explored whether certain microbial signatures could serve as noninvasive diagnostic biomarkers for GD, and assessed the potential mechanistic links between gut microbiota alterations and the pathogenesis of autoimmune thyroid disease.

Who was studied?

The study population comprised 45 untreated GD patients (12 males, 33 females; ages 16–65, median age 37) and 59 healthy control volunteers (22 males, 37 females; ages 22–71, median age 43). Controls were matched for age and sex, and all participants were recruited from the same hospital in Shanghai, China. Inclusion criteria for GD were based on ATA guidelines and included elevated thyroid hormone levels, decreased TSH, diffuse thyroid enlargement by ultrasonography, and positive TRAB antibodies. All subjects were free from malignancy, gastrointestinal, or other endocrine diseases, and had not used antibiotics, probiotics, or prebiotics for at least one month prior to sampling. Fecal samples were collected after overnight fasting, and comprehensive thyroid function and antibody profiles were measured for all participants.

Most important findings

The most notable microbiome-related findings were a significant reduction in alpha diversity and abundance of specific gut microbiota in GD patients compared to controls. At the phylum level, GD patients exhibited a lower proportion of Firmicutes and a higher proportion of Bacteroidetes. At the genus level, GD patients had increased Bacteroides and Lactobacillus but decreased abundances of Blautia, [Eubacterium]_hallii_group, Anaerostipes, Collinsella, Dorea, unclassified_f_Peptostreptococcaceae, and [Ruminococcus]_torques_group. Subgroup analyses indicated that Lactobacillus may play a key role in the pathogenesis of autoimmune thyroid disease, with higher levels observed in GD patients with concurrent Hashimoto’s thyroiditis. Correlation analyses revealed that Blautia levels positively correlated with TPOAB and TMAB levels, suggesting a possible anti-inflammatory, regulatory function; conversely, Bacteroides levels negatively correlated with these antibodies, and Dorea showed a negative correlation with TPOAB. Functional predictions showed that Blautia was strongly associated with multiple metabolic pathways, implicating its role in energy and immune regulation. A diagnostic model using the top nine discriminative genera achieved an AUC of 0.81, indicating strong potential for microbial biomarkers in GD diagnosis.

Key implications

These findings suggest that gut microbiota dysbiosis—characterized by decreased Firmicutes and butyrate-producers, and increased Bacteroides and Lactobacillus—may contribute to the pathogenesis of Graves’ disease through impaired intestinal barrier function, altered immune regulation, and disrupted metabolic signaling. The identified microbial shifts, particularly the reduction of butyrate-producing bacteria such as Blautia and [Eubacterium]_hallii_group, may diminish regulatory T cell differentiation and promote chronic inflammation and autoimmunity. The strong diagnostic potential of a nine-genera microbiome signature offers a promising, noninvasive approach for distinguishing GD patients from healthy individuals. Clinically, the study highlights the potential for microbiome-based diagnostics and therapeutics in GD, but also underscores the need for further mechanistic and longitudinal research to validate causality and therapeutic targets.