Background: Gut microbiota are considered to be intrinsic regulators of thyroid autoimmunity. We designed a cross-sectional study to examine the makeup and metabolic function of microbiota in Graves' disease (GD) patients, with the ultimate aim of offering new perspectives on the diagnosis and treatment of GD. Methods: The 16S ribosomal RNA (rRNA) V3-V4 DNA regions of microbiota were obtained from fecal samples collected from 45 GD patients and 59 controls. Microbial differences between the two groups were subsequently analyzed based on high-throughput sequencing. Results: Compared with controls, GD patients had reduced alpha diversity (p < 0.05). At the phylum level, GD patients had a significantly lower proportion of Firmicutes (p = 0.008) and a significantly higher proportion of Bacteroidetes (p = 0.002) compared with the controls. At the genus level, GD patients had greater numbers of Bacteroides and Lactobacillus, although fewer Blautia, [Eubacterium]_hallii_group, Anaerostipes, Collinsella, Dorea, unclassified_f_Peptostreptococcaceae, and [Ruminococcus]_torques_group than controls (all p < 0.05). Subgroup analysis of GD patients revealed that Lactobacillus may play a key role in the pathogenesis of autoimmune thyroid diseases. Nine distinct genera showed significant correlations with certain thyroid function tests. Functional prediction revealed that Blautia may be an important microbe in certain metabolic pathways that occur in the hyperthyroid state. In addition, linear discriminant analysis (LDA) and effect size (LEfSe) analysis showed that there were significant differences in the levels of 18 genera between GD patients and controls (LDA >3.0, all p < 0.05). A diagnostic model using the top nine genera had an area under the curve of 0.8109 [confidence interval: 0.7274-0.8945]. Conclusions: Intestinal microbiota are different in GD patients. The microbiota we identified offer an alternative noninvasive diagnostic methodology for GD. Microbiota may also play a role in thyroid autoimmunity, and future research is needed to further elucidate the role.

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The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3′-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.