Exploring the causal relationship between gut microbiota and Tourette syndrome based on Mendelian randomization
Hu Zhengyun, Zhang Tao, Hong Xianhui, et al
1.Department of Pediatrics, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; 2. Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Objective To investigate the causal relationship between gut microbiota and Tourette syndrome (TS) using a Mendelian randomization (MR) approach. Methods Genetic data of human gut microbiota were obtained from the MiBioGen consortium, identifying 196 microbial taxa (including 9 phyla, 16 classes, 20 orders, 32 families and 119 genera) as exposure variables to construct robust MR instrumental variables. Genome-wide association study (GWAS) data for TS were incorporated, the causal relationships between gut microbiota and TS were comprehensively assessed using inverse-variance weighted (IVW), MR-Egger regression, weighted median estimator (WME), weighted mode (WM), and simple mode (SM) methods. Statistical robustness was evaluated through Cochran's Q test for heterogeneity, MR-Egger regression test for horizontal pleiotropy, and MR-PRESSO for outlier detection and removal. Results Among 112 single nucleotide polymorphisms (SNPs) selected as instrumental variables, the abundance of the Bifidobacterium was significantly negatively correlated with TS (OR=0.980, 95% CI : 0.975–0.985, P=1.141×10-14). Conclusions There is a negative causal effect between the abundance of the Bifidobacterium and TS. This study validates that Bifidobacterium may participate in the pathogenesis and progression of TS via the gut-brain axis, immunomodulatory mechanisms, and neurotransmitter metabolism providing novel genetic-epidemiological evidence for subsequent research on gut microbiota intervention and probiotic related studies.