Modulation of Gut Microbiota in Graves' Orbitopathy: Prevotella Dominance and Atorvastatin's Impact

We performed fecal microbiota sequencing using the 16S rRNA method on patients with GO (n=48), Graves' disease (GD, n=40), and healthy controls (HC, n=36). Subsequently, fecal samples from patients with GO, GD, and healthy donors were transplanted into antibiotic-treated pseudo-germ-free mice. Finally, the 48 patients with GO were randomly divided into two groups: one group received intravenous glucocorticoids (ivGC) and atorvastatin (n=24), while the other group received ivGC only (n=24), to observe the effects of atorvastatin on GO progression and its impact on gut microbiota. Results: Patients with GO exhibit a distinct gut microbiota composition, particularly marked by increased levels of Prevotella and Bacteroides, compared to patients with GD and HC. Correlation analysis revealed a direct positive association between Prevotella and thyrotropin receptor antibody levels. Pseudo-germ-free mice that received fecal transplants from patients with GO exhibited a significant reduction in body weight, and clear impairment of intestinal barrier integrity. A combined treatment regimen of ivGCs and atorvastatin significantly lowered the clinical activity score in patients with GO, while also promoting a healthier gut microbiota composition and a reduction in Prevotella levels. Conclusions: Gut microbiota imbalance, particularly involving Prevotella, contributes to GO's development and progression. Atorvastatin may slow GO progression by correcting dysregulated gut microbiota, especially reducing Prevotella.