Exploring the causal link between microbiota and tic disorders: a gene sequencing and Mendelian randomization approach

Background Tic disorders (TD), including Tourette syndrome (TS), are common childhood-onset neurodevelopmental conditions with unclear etiology. Emerging observational data suggest that gut-microbiota (GM) dysbiosis accompanies TD, but causality is unresolved. We aimed to determine whether specific bacterial genera are causally implicated in TD susceptibility. Methods Two-sample Mendelian randomization (MR) was performed by integrating the largest available GM genome-wide association study (GWAS) (18,340 Europeans, 211 taxa) with the PGC-TS-2019 GWAS (4,819 cases/9,488 controls). Inverse-variance-weighted estimates were complemented with sensitivity analyses and reverse-MR. Findings were validated in an independent pediatric case–control cohort (10 TD vs seven healthy children) profiled by 16S rRNA V3–V4 sequencing; between-group differences were tested with the Mann–Whitney U test. Results Genetically predicted abundance of Anaerotruncus, Butyrivibrio and Ruminococcaceae UCG-002 conferred protection against TS (OR 0.69–0.86, p = 0.014–0.016), whereas Dialister and Ruminiclostridium 6 increased risk (OR 1.28–1.32, p = 0.030–0.041); Sutterella showed no causal effect ( p = 0.103). No heterogeneity, directional pleiotropy or reverse causation was detected. Sequencing analyses mirrored MR directions: TD cases exhibited significantly lower relative abundance of the protective genera and higher levels of risk taxa compared with controls ( p < 0.05). Conclusions By integrating unbiased genetic instrumentation with targeted microbiome profiling, this study offers exploratory evidence suggesting that specific gut bacteria may be associated with TD pathogenesis. Ruminococcaceae UCG-002 , Anaerotruncus , and Butyrivibrio emerge as potentially protective taxa, while Dialister and Ruminiclostridium 6 may represent candidate risk markers. These preliminary, mechanistically grounded insights should be considered exploratory and may inform future, larger-scale microbiome-directed precision interventions in TD.