New insight into the causal relationship between Graves’ disease liability and drug eruption: a Mendelian randomization study

BackgroundGraves’ disease (GD) and drug eruption are closely associated and frequently observed in the clinical setting. However, it remains unclear whether a causal relationship exists between these two conditions. The aim of the study is to investigate whether GD is causal to drug eruptions using two-sample Mendelian randomization.MethodsWe launched a two-sample MR to investigate whether GD is causal to drug eruption using Genome-wide association study (GWAS) summary data from Biobank Japan and FinnGen. Genetic variants were used as instrumental variables to avoid confounding bias. Statistical methods including inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO were conducted to identify the robustness of the causal effect.ResultsGenetically predicted GD may increase the risk of drug eruption by 30.3% (OR=1.303, 95% CI 1.119-1.516, p<0.001) in the Asian population. In European populations, GD may increase the generalized drug eruption by 15.9% (OR=1.159, 95%CI 0.982-1.367, p=0.080).ConclusionsWe found GD is potentially causal to drug eruption. This finding expanded the view of the frequently observed co-existence of GD and adverse drug reactions involving the skin. The mechanism remains for further investigation

Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice

Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman’s correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis