Faecalibacterium prausnitzii alleviates Graves' orbitopathy by modulating short-chain fatty acid (SCFA) metabolism and inhibiting orbital fibrosis and adipogenesis.

Graves' orbitopathy (GO) is an autoimmune inflammatory disorder characterized by orbital fibrosis and adipose tissue expansion, leading to proptosis and ocular dysfunction. Recent evidence suggests that gut microbiota dysbiosis contributes to GO pathogenesis, particularly through alterations in short-chain fatty acid (SCFA) metabolism. This study investigated the role of Faecalibacterium prausnitzii (F. prausnitzii), a key butyrate-producing bacterium, in modulating GO-related fibrosis and adipogenesis. Clinical fecal sample analysis revealed a significant reduction in F. prausnitzii abundance in GO patients. In a murine GO model, oral administration of F. prausnitzii significantly alleviated periorbital swelling, suppressed collagen deposition, and reduced lipid accumulation in orbital tissues. The metabolomic analysis demonstrated that F. prausnitzii restored butyrate levels, which were significantly depleted in GO. In vitro, butyrate treatment inhibited TGF-β-induced fibrosis and adipogenesis in orbital fibroblasts by downregulating α-SMA, collagen I, PPARγ, and C/EBPα expression. Additionally, F. prausnitzii administration improved thyroid function by reducing thyroid hormone and autoantibody levels. These findings highlight the therapeutic potential of F. prausnitzii in GO through modulation of gut microbiota-derived SCFA metabolism, suppression of fibroblast activation, and inhibition of adipogenic differentiation, providing a promising microbiota-based intervention for GO management.