Gut microbiome and serum metabolome alterations in isolated dystonia

Background: Dystonia is a complex neurological movement disorder characterised by involuntary muscle contractions. The relationship between the gut microbiota and isolated dystonia remains poorly explored. Methods: We collected faeces and blood samples to study the microbiome and the serum metabolome from a cohort of 57 drug-naive isolated dystonia patients and 27 age- and environment-matched healthy individuals. We first sequenced the V4 regions of the 16S rDNA gene from all faeces samples. Further, we performed metagenomic sequencing of gut microbiome and non-targeted metabolomics profiling of serum from dystonia patients with significant dysbiosis. Findings: Gut microbial β - diversity was significantly different, with a more heterogeneous community structure among dystonia individuals than healthy controls, while no difference in α-diversity was found. Gut microbiota in dystonia patients was enriched with Blautia obeum, Dorea longicatena and Eubacterium hallii, but depleted with Bacteroides vulgatus and Bacteroides plebeius. Metagenomic sequencing revealed that genes related to the citrate cycle, vitamin B6 and glycan metabolism were less abundant in dystonia, while genes linked to purine and tryptophan biosynthesis were more abundant. Serum metabolome analysis revealed altered levels of tyrosine and glutamate. The integrative analysis of the gut microbiome and serum metabolomics identified dystonia-associated gut microbial species linked to changes in serum metabolites, reflecting the effect of the gut microbiome on metabolic activity in isolated dystonia. Interpretation: This study is the first to reveal gut microbial dysbiosis in dystonia patients. Our findings identified previously unknown links between intestinal microbiota alterations, circulating amino acids and dystonia, providing new insight into the pathogenesis of isolated dystonia. Funding Statement: This research was supported by the Beijing Natural Science Foundation (No.7164254), the CAMS Innovation Fund for Medical Sciences (2017-I2M-3-017). Declaration of Interests: We have no conflicts of interest. Ethics Approval Statement: Written informed consent was obtained from all individuals. The study was approved by the ethics committees of Beijing Tiantan Hospital.