Exploring gut microbiota and metabolite alterations in patients with thyroid-associated ophthalmopathy using high-throughput sequencing and untargeted metabolomics

Front Endocrinol (Lausanne). 2024 Jul 29:15:1413890. doi: 10.3389/fendo.2024.1413890. eCollection 2024.

Abstract

Introduction: Thyroid-associated ophthalmopathy (TAO) is an autoimmune-driven orbital inflammatory disease. Despite research efforts, its exact pathogenesis remains unclear. This study aimed to characterize the intestinal flora and metabolic changes in patients with TAO to identify the flora and metabolites associated with disease development.

Methods: Thirty patients with TAO and 29 healthy controls were included in the study. The intestinal flora and metabolites were analyzed using high-throughput sequencing of the 16S rRNA gene and non-targeted metabolomics technology, respectively. Fresh fecal samples were collected from both populations for analysis.

Results: Reduced gut richness and diversity were observed in patients with TAO. Compared to healthy controls, significant differences in relative abundance were observed in patients with TAO at the order level Clostridiales, family level Staphylococcaceae, genus level Staphylococcus, Fournierella, Eubacterium siraeum, CAG-56, Ruminococcus gnavus, Intestinibacter, Actinomyces, and Erysipelotrichaceae UCG-003 (logFC>1 and P<0.05). Veillonella and Megamonas were closely associated with clinical symptoms in patients with TAO. Among the 184 significantly different metabolites, 63 were upregulated, and 121 were downregulated in patients with TAO compared to healthy controls. The biosynthesis of unsaturated fatty acids was the significantly enriched metabolic pathway. Correlation analysis revealed Actinomyces was positively correlated with NAGlySer 15:0/16:0, FAHFA 3:0/20:0, and Lignoceric Acid, while Ruminococcus gnavu was positively correlated with Cer 18:0;2O/16:0; (3OH) and ST 24:1;O4/18:2.

Conclusion: Specific intestinal flora and metabolites are closely associated with TAO development. Further investigation into the functional associations between these flora and metabolites will enhance our understanding of TAO pathogenesis.

Keywords: high throughput sequencing; intestinal flora; metabolite alterations; thyroid-associated ophthalmopathy; untargeted metabolomics.

MeSH terms

  • Adult
  • Case-Control Studies
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Graves Ophthalmopathy* / genetics
  • Graves Ophthalmopathy* / metabolism
  • Graves Ophthalmopathy* / microbiology
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Male
  • Metabolome
  • Metabolomics* / methods
  • Middle Aged
  • RNA, Ribosomal, 16S / genetics

Substances

  • RNA, Ribosomal, 16S

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Scientific Research Project of Shanxi Provincial Health Commission (2021XM46); the Natural Science Research Project of Shanxi Provincial Department of Science and Technology (20210302123343); Hospital fund of Shanxi Eye Hospital (C202201), (B202201), (Q202203).