Comparative assessment of gut microbial composition and function in patients with Graves’ disease and Graves’ orbitopathy

Abstract

Background

A previous study indicated that gut microbiota changed notably in Graves’ orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves’ disease (GD) and GO are unclear.

Objective

The present study aimed to identify specific intestinal bacteria of GD and GO, respectively.

Methods

The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing.

Results

At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family.

Conclusions

This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

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Abbreviations

GO:

Graves’ orbitopathy

GD:

Graves’ disease

HT:

Hashimoto Thyroiditis

TRAb:

Thyrotropin receptor antibody

IBD:

Inflammatory bowel disease

SLE:

Systemic lupus erythematosus

RA:

Rheumatoid arthritis

AITD:

Autoimmune thyroid diseases

TPOAb:

Thyroperoxidase antibody

TGAb:

Antithyroglobulin antibody

OTU:

Operational taxonomy units

KEGG:

Kyoto Encyclopedia of Genes and Genomes

PCoA:

Principal coordinate analysis

LDA:

Linear discriminant analysis

LEfSe:

LDA effect size

MDG:

Mean Decrease Gini

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Acknowledgements

The authors thank all the participants and staff involved in the study.

Funding

This work was supported by the Beijing Municipal Hospital Research and Development Program (PX2016063), the Expert Promotion Program of Beijing Health Systems (2015-3-017) to Zhong Xin, and the Foundation of Beijing Tongren Hospital (2015-YJJ-ZZL-006) to Ting-Ting Shi.

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Correspondence to Z. Xin or L. Hua.

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The study was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University. All procedures were performed in the study in accordance with the 1964 Helsinki declaration and its later amendments.

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Shi, TT., Xin, Z., Hua, L. et al. Comparative assessment of gut microbial composition and function in patients with Graves’ disease and Graves’ orbitopathy. J Endocrinol Invest 44, 297–310 (2021). https://doi.org/10.1007/s40618-020-01298-2

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Keywords

  • Graves’ disease
  • Graves’ orbitopathy
  • Gut microbiota
  • 16S rRNA gene
  • Metabolic functions