Two-sample Mendelian randomization integrated with 16S rRNA sequencing identified specific gut bacterial genera—Anaerotruncus, Butyrivibrio, and Ruminococcaceae UCG-002 as potentially protective and Dialister and Ruminiclostridium 6 as candidate risk taxa—that may be causally associated with tic disorder/Tourette syndrome susceptibility.
Key Findings
Results
Genetically predicted higher abundance of Anaerotruncus, Butyrivibrio, and Ruminococcaceae UCG-002 was associated with reduced risk of Tourette syndrome.
Odds ratios ranged from 0.69 to 0.86 for these three protective genera.
Statistical significance ranged from p = 0.014 to p = 0.016.
MR was performed using the largest available GM GWAS (18,340 Europeans, 211 taxa) integrated with the PGC-TS-2019 GWAS (4,819 cases/9,488 controls).
Inverse-variance-weighted estimates were the primary method, complemented by sensitivity analyses.
Results
Genetically predicted higher abundance of Dialister and Ruminiclostridium 6 was associated with increased risk of Tourette syndrome.
Odds ratios ranged from 1.28 to 1.32 for these two risk-associated genera.
Statistical significance ranged from p = 0.030 to p = 0.041.
Sutterella showed no statistically significant causal effect (p = 0.103).
No heterogeneity or directional pleiotropy was detected in sensitivity analyses.
Results
No evidence of reverse causation was detected in reverse-MR analyses.
Reverse-MR was conducted to test whether tic disorder genetically influences gut microbiota abundance.
No significant reverse causal effects were identified for any of the taxa examined.
This supports the directionality of the causal estimates from gut microbiota to TD susceptibility.
Results
Independent 16S rRNA sequencing of a pediatric cohort corroborated the MR-identified directions of association.
The cohort comprised 10 TD cases versus 7 healthy children.
Between-group differences were tested with the Mann-Whitney U test.
TD cases exhibited significantly lower relative abundance of the protective genera (Anaerotruncus, Butyrivibrio, Ruminococcaceae UCG-002) compared with controls (p < 0.05).
TD cases exhibited significantly higher relative abundance of risk taxa (Dialister and Ruminiclostridium 6) compared with controls (p < 0.05).
Sequencing targeted the V3-V4 hypervariable region of the 16S rRNA gene.
Methods
The Mendelian randomization design used genetic instruments from a GWAS of 211 gut microbial taxa in 18,340 European individuals.
The GM GWAS represented the largest available at the time of analysis.
The TS outcome GWAS (PGC-TS-2019) included 4,819 cases and 9,488 controls.
The two-sample MR framework was used to minimize confounding inherent in observational studies.
Sensitivity analyses complemented the primary inverse-variance-weighted estimates.
Conclusions
The study characterizes its findings as exploratory evidence that specific gut bacteria may be associated with TD pathogenesis.
Authors describe the insights as 'preliminary, mechanistically grounded' and state they 'should be considered exploratory.'
The paper calls for 'future, larger-scale microbiome-directed precision interventions in TD.'
The pediatric validation cohort was small (n = 17 total), limiting generalizability.
The authors note that causality is 'unresolved' in prior observational data and frame this study as addressing that gap.
Wu G, Wang M, Si Y, Wang X, Li H, Wang L, et al.. (2026). Exploring the causal link between microbiota and tic disorders: a gene sequencing and Mendelian randomization approach.. PeerJ. https://doi.org/10.7717/peerj.20812