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Objective: The relationship between gut microbiome and trimethylamine oxide (TMAO) has not been fully elucidated. We aimed to assess the causal effects of different gut microbes on TMAO using Mendelian randomization (MR)., Methods: Gut microbiome and TMAO datasets were acquired from genome-wide association studies and screened for single nucleotide polymorphisms according to the basic assumptions of MR. Inverse variance weighted was used as the main method in MR analysis to assess the causal relationship between the gut microbiome and TMAO. Finally, the MR-Egger intercept, Cochran's Q test, and leave-one-out sensitivity analysis were used to assess the horizontal pleiotropy, heterogeneity, and robustness of the results, respectively., Results: MR analysis revealed that the species Bacteroides finegoldii (odds ratio [OR] 1.064, 95% confidence interval [CI] 1.003 to 1.128, p = 0.039), family Sutterellaceae (OR 1.188, 95% CI 1.003 to 1.407, p = 0.047), and phylum Pseudomonadota (OR 1.205, 95% CI 1.036 to 1.401, p = 0.016), as well as the species Bacteroides uniformis (OR 1.263, 95% CI 1.039 to 1.535, p = 0.019), were positively associated with increased genetic susceptibility to TMAO. In contrast, the species Bacteroides thetaiotaomicron (OR 0.813, 95% CI 0.696 to 0.950, p = 0.009) and Bilophila wadsworthia (OR 0.828, 95% CI 0.690 to 0.995, p = 0.044) were associated with reduced genetic susceptibility to TMAO. Additionally, the MR-Egger intercept indicated no horizontal pleiotropy ( p ≥ 0.05), and Cochran's Q test and sensitivity analysis demonstrated that the results were not heterogeneous ( p ≥ 0.05) and were robust., Conclusion: Our findings revealed the role of the phylum Pseudomonadota, family Sutterellaceae, species Bacteroides finegoldii , and Bacteroides uniformis in increasing TMAO, as well as the species Bacteroides thetaiotaomicron and Bilophila wadsworthia in decreasing TMAO. This study provides new insights into the relationship between the gut microbiome and TMAO levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Yin, Deng, Yang, Bai and Yu.)

Objective: This study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR)., Methods: Single nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively., Results: Forward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn's disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran's Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results., Conclusion: This MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bai, Yu, Yang, Hu, Wu, Tong, Yin, Deng, Chen and Tan.)

Objective: This study aimed to explore the clinical efficacy and acupoint combinations of auricular pressure for treating type 2 diabetes., Methods: Eight common databases were searched for publications related to auricular pressure in type 2 diabetes as of November 2023. A meta-analysis was performed to assess the efficacy and safety of auricular pressure therapy. Data mining was used to analyze the core acupoints for auricular pressure., Results: Meta-analysis demonstrated that compared with the conventional treatment group, the combined auricular pressure and conventional treatment group had significantly reduced fasting blood glucose (mean difference [MD]: -0.93; 95% confidence interval [CI]: -1.17 to -0.68; p < 0.00001), 2-hour postprandial blood glucose (MD: -1.58; 95% CI: -2.04 to -1.12; p < 0.00001), glycated hemoglobin A1c (MD: -0.83; 95% CI: -1.19 to -0.48; p < 0.00001), total cholesterol (MD: -0.43; 95% CI: -0.72 to -0.14; p = 0.004), triglycerides (MD: -0.33; 95% CI: -0.64 to -0.03; p < 0.00001), systolic blood pressure (MD: -14.75; 95% CI: -24.46 to -5.05; p = 0.003), diastolic blood pressure (MD: -10.32; 95% CI: -20.14 to -0.50; p = 0.04), and body mass index (MD: -1.74; 95% CI: -2.61 to -0.87; p < 0.0001), while adverse events were comparable (RR: 0.84; 95% CI: 0.43 to 1.66; p = 0.61). Egger's test revealed no publication bias ( p = 0.715). Data mining identified AH 6a , TF 4 , AT 4 , CO 18 , and CO 10 as core acupoints for treating type 2 diabetes with auricular pressure., Conclusion: Auricular pressure safely improves blood glucose and lipid levels, blood pressure, and body mass index in patients with type 2 diabetes. A regimen consisting of AH 6a , TF 4 , AT 4 , CO 18 , and CO 10 is expected to serve as a complementary treatment for type 2 diabetes., Systematic Review Registration: www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=524887, identifier CRD42024524887., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Xiang, Liu, Yin, Bai and Yu.)

Objective: The role of different immune cells in autism spectrum disorders (ASD) is still controversial. The purpose of this study was to evaluate the causal effects of different immune cell phenotypes on ASD via Mendelian randomization (MR)., Methods: Datasets of immune cell phenotypes were obtained from the European Bioinformatics Institute, and datasets of ASD were obtained from the IEU Open GWAS project. Single nucleotide polymorphisms were selected based on the assumptions of association, independence, and exclusivity. Inverse variance weighted was utilized as the main method for MR analysis. MR-Egger was employed to assess the horizontal pleiotropy of the results. Cochran's Q and leave-one-out method were used for heterogeneity analysis and sensitivity analysis of the results, respectively., Results: MR analysis showed that TD CD8br AC [odds ratio (OR), 1.137; 95% confidence interval (CI), 1.031-1.254; p = 0.010], CD8br %leukocyte (OR, 1.142; 95% CI, 1.067-1.223; p < 0.001), CD8br and CD8dim %leukocyte (OR, 1.117; 95% CI, 1.032-1.210; p = 0.006), naive CD8br %T cell (OR, 1.052; 95% CI, 1.004-1.104; p = 0.035), CD28- CD8dim %T cell (OR, 1.097; 95% CI, 1.038-1.158; p < 0.001), CD127- CD8br AC (OR, 1.086; 95% CI, 1.006-1.171; p = 0.034), CD45 on CD8br (OR, 1.059; 95% CI, 1.021-1.099; p = 0.002), CD3 on HLA DR+ CD8br (OR, 1.098; 95% CI, 1.041-1.158; p < 0.001), CD4 on activated Treg (OR, 1.048; 95% CI, 1.001-1.096; p = 0.046), CD3 on CD39+ resting Treg (OR, 1.070; 95% CI, 1.012-1.131; p = 0.018), IgD+ CD38- %lymphocyte (OR, 1.103; 95% CI, 1.023-1.190; p = 0.011), CD62L- plasmacytoid DC %DC (OR, 1.046; 95% CI, 1.001-1.093; p = 0.046), and FSC-A on plasmacytoid DC (OR, 1.075; 95% CI, 1.003-1.153; p = 0.042) were associated with increased genetic susceptibility to ASD. MR-Egger displayed no horizontal pleiotropy ( p ≥ 0.05). Cochran's Q revealed no heterogeneity of results ( p ≥ 0.05). Sensitivity analysis indicated that the results were robust., Conclusion: This MR analysis revealed 13 immune cell phenotypes associated with increased genetic susceptibility to ASD and emphasized the importance of CD8 T cells and Tregs, which provides new directions for the pathogenesis and drug research of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Yang, Hu, Yin and Yu.)

Objective: The effect of tea on gout and uric acid is still controversial. This study aims to analyze the effect of tea intake on genetic predisposition to gout, idiopathic gout, gout due to impairment of renal function as well as uric acid by Mendelian randomization (MR)., Methods: Forty independent single nucleotide polymorphisms (SNPs) associated with tea intake were selected from UK Biobank. SNPs for uric acid were obtained from BioBank Japan, SNPs for gout were obtained from UK Biobank, and SNPs for gout due to impairment of renal function and idiopathic gout were derived from FinnGen. The causal relationship of exposure-outcome was tested using inverse variance weighted, MR-Egger and weighted median. MR-Egger intercept was employed to assess horizontal pleiotropy, Cochran's Q test was used to assess heterogeneity, and leave-one-out sensitivity analysis was utilized to analyze the stability of the results., Results: The results of MR analysis showed that tea intake was negatively associated with gout due to impairment of renal function (OR 0.997, 95% CI 0.994 to 0.999, P = 0.017), whereas there was no causal association with gout, idiopathic gout, and uric acid ( P > 0.05), for which sensitivity analysis suggested that these results were robust., Conclusions: There was a genetic predisposition effect of increased tea intake on the reduced risk of gout due to impairment of renal function, whereas there was no such effect on gout, idiopathic gout, and uric acid. Tea intake may become an important option in the dietary treatment of gout due to impairment of renal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Yang, Hu, Tong, Yin and Yu.)