Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients

Abstract

The gut microbial association with host co-existence is critical for body homeostasis and pathogenicity. Graves' disease (GD) is an autoimmune disease manifested with hyperthyroidism and ophthalmopathy. However, we hypothesized that gut bacteria could affect an important role in GD pathogenicity. The current study aim was to characterize and investigate the intestinal bacterial composition of GD qualitatively and quantitatively. 27 GD and 11 healthy controls were enrolled for fecal sample collection. The PCR-DGGE of 16S rRNA gene by targeting V3 region and Real-time PCR for Lactobacillus, Bifidobacterium, Bacteroides vulgatus and Clostridium leptum, were performed. High-throughput sequencing of 16S rRNA gene with the V3+V4 site was perormed on Hiseq2500 platform on randomly 20 selected samples. The relative analysis of richness indices and diversity illustrated lesser diversification of intestinal bacteria in GD patients in contrast to controls. The data statistics shows the alteration in phyla of GD as compared to control. At the family taxonomic level, the relative abundance of Prevotellaceae and Pasteurellaceae were significantly higher in patients, while Enterobacteriaceae, Veillonellaceae, and Rikenellaceae were significantly lower in the diseased group as compared to control. At the genus level, a significant raised in genera count of the diseased group were Prevotella_9 and Haemophilus, while significantly decreased in the genera of the GD group were Alistipes and Faecalibacterium. The modulation in intestinal bacterial composition was checked at species level particularly H. parainfluenza abundance was raised in GD. The outcomes of the current study are aligned with the proposed hypothesis of gut microbial dysbiosis in GD. Statistically, alpha indices and differential abundance analyses of each intestinal bacterial community were significantly changed in GD. Therefore, the current study may provide a new insight into the GD pathogenesis and, in turn, explore its contribution in possible treatments.

Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients

“…This finding is consistent with previous studies investigating the gut microbiota in HT and hyperthyroidism patients. 23,24 However, the opposite results were recently found in patients with GD with/without ophthalmopathy 28 and an animal model of hyperthyroidism. 25 In addition, a decrease in the diversity of the microbiota is associated with several diseases, such as liver cancer, 42 diabetes mellitus type 1 (T1D) 43 and ankylosing spondylitis (AS).…”

“…In our previous study, the gut microbiota alpha diversity (richness and diversity) in HT patients was higher than that in HCs, although the differences were nonsignificant ( p > 0.05) . However, in recent hyperthyroidism studies, the authors noted that the gut microbiota alpha diversity was lower in hyperthyroidism patients or mouse models than in HCs . A Venn diagram showing the overlapping OTU data of the groups was constructed to better evaluate the shared richness.…”

“…24 However, in recent hyperthyroidism studies, the authors noted that the gut microbiota alpha diversity was lower in hyperthyroidism patients or mouse models than in HCs. 25,28 A Venn diagram showing the overlapping OTU data of the groups was constructed to better evaluate the shared richness. This analysis revealed that 853 of the 2845 OTUs accounting for the total richness were common to all samples; therefore, approximately 620 and 1372 OTUs were identified in HC and TC patient samples, respectively ( Fig.…”

“…Finally, gut dysbiosis could disturb the finely tuned immune balance and disrupt the tolerance to self‐antigens and nonpathogenic nonself‐antigens, leading to the development of autoimmune disorders. Fortunately, the relationship between autoimmune thyroid diseases (AITD) and the gut microbiota has received much attention …”

“…Fortunately, the relationship between autoimmune thyroid diseases (AITD) and the gut microbiota has received much attention. 23,24,28 In contrast, extensive metabolomics studies have used different samples from TC patients, including thyroid tissue, serum, exhaled breath and urine. [29][30][31][32][33][34] Changes in the concentrations of lipids (linolenic acid and sphingomyelin), galactinol and inosine were identified by TC tissue metabolic profiling.…”