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Background and Objective   A previous study reported alterations in the intestinal microbiota in patients with Graves' orbitopathy (GO). Thyrotropin receptor autoantibody (TRAb) stimulates orbital and periorbital tissues and plays a pivotal role in the development of GO. However, the association between gut microbiota and TRAb in GO patients has still remained elusive. In this study, we explored the relationships between gut microbiota and GO-related traits, in which we applied a metabolic-network-driven analysis to identify GO trait-related modules and extracted significant operational taxonomic units (OTUs).Methods   In the present study, we profiled gut microbiota using 16S rRNA gene sequencing in 31 GO patients. We performed metabolic-network-driven analysis to investigate the association between gut microbiota and GO-related traits (e.g., TRAb, TGAb, and TPOAb) in the combination of microbial effects.Results   Applying microbiome network analysis of cooccurrence patterns and analysis of topological properties, we found that  s_Prevotella_copri  and  f_Prevotellaceae  showed a significant correlation with TRAb. In particular, we applied the latent class model to explore the association between gut microbiota and GO-related traits in the combination of microbial effects. It was revealed that the subjects involved in the latent class model with the higher abundance of  s_Prevotella_copri  and  g_Bacteroides  had a higher TRAb level.Conclusions   Our results revealed the potential relationships between gut microbiota and GO-related traits in the combination of microbial effects. This study may provide a new insight into the interaction between the intestinal microbiota and TRAb-associated immune responses in GO patients.

The Potential Link between Gut Microbiota and Serum TRAb in Chinese Patients with Severe and Active Graves’ Orbitopathy