Objective: To detect gut microbial signatures of Tourette syndrome (TS) in the first sibling-controlled investigation of this condition.

Background: The contribution of gut microbiome, and its interaction with other key factors like diet and host genetics, in TS are poorly understood.

Method: 33 patients aged 7–16 years with TS (24 males) and paired unaffected siblings aged 5–18 years (13 males) were recruited from the Tourette and Pediatric Movement Disorders Clinic, Alberta Children’s Hospital, Calgary. Shotgun metagenomic sequencing was performed on stool specimens, with taxonomic and functional profiles obtained from MetaPhlAn3 and HUMAnN3. Community ecology metrics and non-parametric correlations were evaluated using phyloseq, and differential abundance analyses were conducted with DESeq2 and ANCOM-BC (FDR <0.05).

Results: Alpha diversity by Shannon and Chao 1 indices, and beta diversity by Bray-Curtis’s dissimilarity index did not statistically differ between patients and siblings. Permutational multivariate analysis of variance demonstrated that age (P= 0.027), hyperactivity in ADHD (P=0.04) and depression (P=0.015) are associated with variation of the bacterial community in TS patients. Tic severity inversely related to Akkermansia mucinophila (ρ=-0.365, P=0.037), and positively to Enterorhabdus caecimuris (ρ=0.402, P=0.020), Intestinomonas butyriciproducens (ρ=0.371, P=0.034) and Bilophila wadsworthia (ρ=-0.348, P=0.047). Sex-adjusted DeSeq2 differential abundance analysis detected 6 bacterial species enriched in TS children relative to siblings and 2 depleted, all low prevalence taxa (20–33%). Among these were three enriched species previously linked to neuropsychiatric disorders: Clostridium bolteae, Desulfovibrio piger and Erysipelatoclostridium ramosum. Differentially abundant genes in children with TS identified increases in genes involved in protein, fatty acid and bile acid metabolism.

Conclusion: This pilot study revealed minimal differences between the gut microbiome of TS patients and their sibling pairs, highlighting both the benefit of a well-controlled sibling-pair design and the need for a larger sample size. Two new hypotheses were generated: 1) pro-inflammatory bacteria may correlate with tic symptom severity more than TS diagnosis; and 2) bile acid dysregulation may contribute to metabolic disturbances affecting the gut-brain axis in TS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/metagenomic-exploration-of-the-gut-microbiome-in-a-sibling-controlled-pilot-study-of-children-with-tourette-syndrome/