Gut Microbiome Signatures in Graves’ and Hashimoto’s Disease: Microbial Markers and ABC Transporter Pathway Insights Original paper

What was studied?

This study investigated the alterations in gut microbiota composition and function in patients with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), the two most common forms of autoimmune thyroid disease (AITD). The authors collected fecal samples from patients with GD, HT, and healthy controls, analyzing the gut microbial communities through 16S rRNA sequencing. Thyroid function and autoantibody levels were measured to confirm disease status. Furthermore, the study employed advanced bioinformatics analyses, including LEfSe (Linear Discriminant Analysis Effect Size), random forest modeling, and functional pathway predictions using KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) databases. The primary aim was to identify specific microbial taxa and metabolic pathways associated with GD and HT, and to explore whether common microbial or metabolic signatures could differentiate patients from healthy individuals. The authors also sought to uncover functional shifts in gut microbial metabolism potentially relevant to AITD pathogenesis.

Who was studied?

The study enrolled 70 Han Chinese adults from northeast China: 27 patients with GD, 27 patients with HT, and 16 healthy controls. All patients were newly diagnosed, had not received anti-thyroid or hormone replacement therapy, and were free from other autoimmune diseases, recent antibiotic or probiotic use, metabolic disorders, and significant surgeries affecting the gastrointestinal tract. The control group had normal thyroid function and negative thyroid antibodies. All participants underwent standardized clinical, laboratory, and microbiological assessments. The strict inclusion and exclusion criteria ensured minimal confounding from comorbidities or medication use, and the cohort represents a relatively homogenous ethnic and geographic background, enhancing internal validity though potentially limiting generalizability.

Most important findings

The study revealed that although the overall abundance and diversity of gut microbiota were similar between GD, HT, and healthy controls, the structure and composition of the microbial communities were markedly different in patients with autoimmune thyroid disease. Notably, HT patients had the highest levels of Proteobacteria and Actinobacteria, with these phyla also elevated in GD compared to controls. Both GD and HT groups exhibited increased levels of Erysipelotrichia, Cyanobacteria, and Ruminococcus_2, while Bacillaceae and Megamonas were depleted relative to controls. At the genus level, Prevotella_9, Ruminococcus_2, and Lachnospiraceae_NK4A136_group were elevated in GD, and Enterococcus was elevated in HT, while Megamonas was more abundant in healthy individuals. Random forest analysis identified Bacillus, Blautia, and Ornithinimicrobium as potential biomarkers for distinguishing GD and HT from healthy controls, with high discriminative accuracy (AUC up to 1). Functional prediction analyses indicated that the “ABC transporter” metabolic pathway—a key system for ATP-dependent substrate transport—was enriched in both disease groups, suggesting its involvement in disease pathogenesis. GD and HT patients also showed greater microbial enrichment in carbohydrate transport/metabolism and a reduction in amino acid transport/metabolism. Furthermore, unique and shared bacterial taxa were linked to metabolic pathways such as glutathione, arachidonic acid, purine, and pyrimidine metabolism, implicating these pathways in the autoimmune process.

Key implications

This study provides evidence that patients with GD and HT share a common dysbiotic gut microbiome signature and functional metabolic alterations, particularly involving the ABC transporter pathway and several key bacterial taxa. These findings suggest that gut microbiome changes may contribute to the pathogenesis of AITD through disruption of specific microbial communities and metabolic pathways. Identification of Bacillus, Blautia, and Ornithinimicrobium as potential diagnostic biomarkers could facilitate early detection or risk stratification of AITD based on stool microbiome analysis. The enrichment of the ABC transporter pathway points to potential mechanistic links between gut microbiota metabolism and thyroid autoimmunity and may offer new therapeutic targets. The results support the concept of a “thyroid-gut axis,” where microbial and metabolic profiles are intimately associated with thyroid autoimmunity. However, the study’s limitations, including its single-center design and ethnically/geographically homogenous cohort, highlight the need for larger, diverse, and mechanistic studies to confirm and expand upon these findings.