Abstract

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.

Highlights

  • Graves’ orbitopathy (GO) is an autoimmune disease, commonly associated with Graves’ disease (GD)

  • Our study provided a framework to better perceive the interactions of gut microbiota and extracted the important bacteria associated with thyrotropin receptor autoantibody (TRAb)

  • We found only five bacteria: s_Prevotella_copri (OTU_2), s_Bacteroides_stercoris (OTU_5), g_Bacteroides (OTU_736), f_Prevotellaceae (OTU_1068), and g_Bacteroides (OTU_1112), which showed a significant correlation with GO-related traits, such as clinical activity score (CAS), TRAb, and TGAb (Figure 5(b))

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Summary

Introduction

Graves’ orbitopathy (GO) is an autoimmune disease, commonly associated with Graves’ disease (GD). It influences appearance, visual acuity, and even quality of life of patients [1,2,3]. A recently conducted study demonstrated that gut microbiota is associated with some thyroid diseases, including Hashimoto’s thyroiditis (HT) and GD [6]. Et al reported that high titers of TRAb are related to thyroid-associated orbitopathy in patients with GD [13].

Study Subjects and Methods
Network Analysis
Results
Correlation between GO-Related Traits and Gut Microbiota
Discussion

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