Graves’ Disease is the most common organ-specific autoimmune disease and has been linked in small pilot studies to taxonomic markers within the gut microbiome. Important limitations of this work include small sample sizes and low-resolution taxonomic markers. Accordingly, we studied 162 gut microbiomes of mild and severe Graves’ disease (GD) patients and healthy controls. Taxonomic and functional analyses based on metagenome-assembled genomes (MAGs) and MAG-annotated genes, together with predicted metabolic functions and metabolite profiles, revealed a well-defined network of MAGs, genes and clinical indexes separating healthy from GD subjects. A supervised classification model identified a combination of biomarkers including microbial species, MAGs, genes and SNPs, with predictive power superior to models from any single biomarker type (AUC = 0.98). Global, cross-disease multi-cohort analysis of gut microbiomes revealed high specificity of these GD biomarkers, notably discriminating against Parkinson’s Disease, and suggesting that non-invasive stool-based diagnostics will be useful for these diseases.

Liraglutide protects cardiomyocytes from high glucose-induced apoptosis by activating the Epac-1/Akt pathway.

Graves’ disease (GD) is an autoimmune disorder that frequently results in hyperthyroidism and other symptoms. Here, we designed a 6-month study with patients divided into three treatment groups, namely, methimazole (MI, n = 8), MI + black bean (n = 9) and MI + probiotic Bifidobacterium longum (n = 9), to evaluate the curative effects of probiotics supplied with MI on thyroid function of patients with GD through clinical index determination and intestinal microbiota metagenomic sequencing. Unsurprisingly, MI intake significantly improved several thyroid indexes but not the most important thyrotropin receptor antibody (TRAb), which is an indicator of the GD recurrence rate. Furthermore, we observed a dramatic response of indigenous microbiota to MI intake, which was reflected in the ecological and evolutionary scale of the intestinal microbiota. In contrast, we did not observe any significant changes in the microbiome in the MI + black bean group. Similarly, the clinical thyroid indexes of patients with GD in the probiotic supplied with MI treatment group continued to improve. Dramatically, the concentration of TRAb recovered to the healthy level. Further mechanistic exploration implied that the consumed probiotic regulated the intestinal microbiota and metabolites. These metabolites impacted neurotransmitter and blood trace elements through the gut-brain axis and gut-thyroid axis, which finally improved the host’s thyroid function.

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Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

Men and women are sexually dimorphic but whether common anthropometric and biochemical parameters predict type 2 diabetes (T2D) in different ways has not been well studied. Here we recruit 1579 participants in Hainan Province, China, and group them by sex. We compared the prediction power of common parameters of T2D in two sexes by association, regression, and Receiver Operating Characteristic (ROC) analysis. HbA1c is associated with FPG stronger in women than in men and the regression coefficient is higher, consistent with higher prediction power for T2D. Age, waist circumference, BMI, systolic and diastolic blood pressure, triglyceride levels, total cholesterol, LDL, HDL, fasting insulin, and proinsulin levels all predict T2D better in women. Except for diastolic blood pressure, all parameters associate or tend to associate with FPG stronger in women than in men. Except for diastolic blood pressure and fasting proinsulin, all parameters associate or tend to associate with HbA1c stronger in women than in men. Except for fasting proinsulin and HDL, the regression coefficients of all parameters with FPG and HbA1c were higher in women than in men. Together, by the above anthropometric and biochemical measures, T2D is more readily predicted in women than men, suggesting the importance of sex-based subgroup analysis in T2D research.

Diabetes mellitus is a kind of highly prevalent chronic disease in the world. The intervention measures on the risk factors of prediabetes contribute to control and reduce the occurrence of diabetes. This study aimed to investigate the correlation between proinsulin (PI), true insulin (TI), PI/TI, 25(OH) D3, waist circumference (WC), and risk of prediabetes. Methods In this cross-sectional study, 1662 subjects including 615 prediabetes and 1047 non-prediabetes were recruited. Spearman's correlation analysis was used to explore the association of PI, TI, PI/TI, 25(OH) D3, and waist circumference with prediabetes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Receiver-Operator Characteristic (ROC) curve was used to evaluate the risk of prediabetes. Results Our study showed that FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC could enhance the risk of prediabetes (OR 1.034; OR 1.007; OR 1.005; OR 1.002; OR 3.577, OR 1.053, respectively; all p< 0.001). Stratified analyses indicated that FPI/FTI associated with an increased risk of prediabetes in men (OR 2.080, p = 0.042). FTI have a weak association with prediabetes risk in men and women (OR 0.987, p = 0.001; OR 0.994, p = 0.004, respectively). 2hPI could decrease prediabetes in women (OR 0.995, p = 0.037). Interesting, the sensitivity (86.0%) and AUC (0.942, p< 0.001) of combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) were higher than the diagnostic value of these alone diagnoses. The optimal cutoff point of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC for indicating prediabetes were 15.

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