Dataset Information

Gut Microbiome Composition in Dystonia Patients.

ABSTRACT: Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut-brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of Ruminococcus torques and Dorea formicigenerans, and a lower abundance of Butyrivibrio crossotus compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut-brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.

SUBMITTER: Timmers ER

PROVIDER: S-EPMC9916458 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Gut Microbiome Composition in Dystonia Patients.

Timmers Elze R ER Swarte J Casper JC Gacesa Ranko R Björk Johannes R JR Weersma Rinse K RK Tijssen Marina A J MAJ de Koning Tom J TJ Harmsen Hermie J M HJM Niezen-Koning Klary E KE

International journal of molecular sciences 20230125 3

Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut-brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active ...[more]

PMID: 36768705

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Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

Project description:Gut microbiome (GMB) disturbance can induce chronic low-grade inflammation, which is closely related to the occurrence and development of osteoarthritis (OA). However, the relationship between GMB and OA remains unclear. In this study, we collected stool samples from OA patients and healthy people, and performed Alpha diversity, Beta diversity, MetaStat, and LEfSe analysis by 16S rRNA sequencing to find out the species with significant difference between the two groups. Random forest analysis was performed to find out biomarkers that could distinguish between OA patients and healthy people. PICRUSt and Bugbase analysis were used to compare the difference in functions and phenotypes. Multivariate linear regression analysis (MaAsLin) was used to adjust for gender, age, and body mass index (BMI). The results showed that there was a significant difference in the overall composition of GMB between the two groups (p = 0.005). After adjusting for gender, age, and BMI, we found that p_Bacteroidota (Q = 0.039), c_Bacteroidia (Q = 0.039), and o_Bacteroidales (Q = 0.040) were enriched in the OA group, while s_Prevotella_copri (Q = 0.001) was enriched in the healthy control group. Prevotella could distinguish between OA patients and healthy people with a better diagnostic power (AUC = 77.5%, p < 0.001, 95% CI: 66.9-88.1%). The functions of DNA transcription, amino acid metabolism (including histidine, lysine, and isoleucine), ATP metabolism, and phospholipid metabolism significantly decreased, while glucose metabolism, protein acetylation, and aspartate kinase activity significantly increased in the OA group. In terms of phenotypes, we found that the relative abundance of aerobic (p = 0.003) and Gram-negative (p < 0.001) was higher in the OA group, while contains mobile elements (p = 0.001) and Gram-positive (p < 0.001) were higher in the healthy control group. Our study preliminarily demonstrated that there were differences in the composition, function, and phenotype of GMB in stool samples between OA patients and healthy people, which provided a novel perspective on further study in OA.

Dataset Information

Gut Microbiome Composition in Dystonia Patients.

Publications

Gut Microbiome Composition in Dystonia Patients.

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