Differential analysis of gut microbiota and metabolites in patients with Graves' disease and combined Helicobacter pylori infection.

BACKGROUND: Graves' disease (GD) is one of the most common organ-specific autoimmune disorders. Current evidence indicates that GD pathogenesis results from complex gene-environment interactions, although the precise mechanisms remain incompletely elucidated. This study aims to investigate effects of environmental factors such as gut microbiota and Helicobacter pylori (H. pylori) infection on the pathogenesis of GD. METHODS: This study enrolled 88 treatment-naïve GD patients and 33 healthy controls. Plasma H.pylori-IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). Varieties of gut microbiota in fecal specimens were examined using 16S rDNA sequencing. Gut metabolites were subjected to untargeted metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS). Differences in gut microbiota composition and metabolites were analyzed between the GD group and the control group, as well as between the H. pylori-positive[H. pylori (+)] subgroup and the H. pylori-negative[H. pylori (-)] subgroup within the GD group. RESULTS: Bacteroidota, f-Lactobacillaceae, and Prevotella-9 demonstrated significantly higher prevalence in the GD group compared to the control group. Clostridium_sensu_stricto_1 and Limosilactobacillus exhibited significantly greater abundance in the GD + H. pylori (+) subgroup compared to the GD + H. pylori (-) subgroup. Compared to the control group, in the GD group pregnanetriol, kynurenic acid, and several metabolites in the tryptophan metabolism pathway (serotonin, kynurenate, xanthurenate, and 3-Methyldioxyindole) increased significantly, while mulberrofuran T and fragransol B decreased. Significantly reduced levels of N-methyltyramine, N-isovalerylglycine, and cafestol were observed in the GD + H. pylori (+) subgroup relative to the GD + H. pylori (-) subgroup. CONCLUSION: Significant differences were identified in both gut microbiota composition and metabolites between the GD group and the control group. Alterations in the gut microbiota are potentially linked to GD pathogenesis via modulation of tryptophan metabolic pathway. Significant differences in both gut microbiota composition and metabolites were identified between the H. pylori (+) subgroup and the H. pylori (-) subgroup within the GD group.