Gut Microbiota in Patients With Moyamoya Disease

Study Overview
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Brief Summary
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This study is to find out the association between gut microbiota and moyamoya disease.

Detailed Description
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Moyamoya disease (MMD) is a rare cerebrovascular disorder, it is a major cause of stroke in children and young adults in Japan, Korea, and China, but its pathogenesis is not yet clear. Dysbiosis of gut microbiota may play a role in the pathological change of MMD. In this research, the investigators would perform metagenomic sequencing to find the characteristics of gut microbiota of MMD and to explore the correlations with metabolic, immune, and clinical symptoms. This research will not only help the understanding of the pathophysiology of MMD, but also may provide a reference for the selection of clinical treatment options.

Official Title
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Gut Microbiota in Patients With Moyamoya Disease

Conditions
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Moyamoya Disease, Gut Microbiota

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MMD by DSA according to the Japanese guidelines published in 2012, Stenosis or occlusion of the terminal internal carotid and the proximal middle and anterior cerebral arteries and unilateral or bilateral involvement Age: 2-60 years old. Exclusion Criteria: Moyamoya syndrome, Pregnancy, Evidence of gastrointestinal infection/ inflammation/ obstruction History of partial or total resection of small or large bowel, as well as gut reanastomosis, Use of antibiotics within 2 weeks prior to symptoms onset, Gastrointestinal malignancy Any hospitalization within 3 months before recruitment

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MMD group<br>Consecutive patients diagnosed with MMD during hospitalization in Beijing Tiantan Hospital, Capital Medical University will be recruited. | |
| Healthy control group<br>Age and sex matched subjects will be invited to join the study as the control. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diversity analysis of genes and species between MMD patients and the control group | Based on the gene and species composition of each sample, the Chao1 and Shannon indexes, as well as the observed OTUs (operational taxonomic units), will be calculated in order to identify the differences in gene and species diversity for each group. | Through study completion，eight months. | 
| Analysis of differences in intestinal microbiota between MMD patients and the control group | The Spearman correlation coefficient between genes will be calculated, and genes with strong correlation will be grouped into one cluster, as a CAG. The abundance of CAGs in each sample will be determined Furthermore, the significantly enriched species in the control and MMD groups will be enumerated for network display. | Through study completion，eight months. | 
| Analysis of functional differences in the intestinal microbiota of MMD patients in comparison to the control group | The LEfSe discriminant analysis will be used to screen for significant differences between groups. The dimensionality reduction will be implemented by LDA, and the impact of function difference will be evaluated to obtain the LDA score and identify significantly different functions between groups. | Through study completion，eight months. | 
| Analysis of metabolites of the intestinal microbiota of MMD patients in comparison to the control group | Metabolites of the intestinal microbiota between two groups | Through study completion，eight months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation analysis between gut microbiota in MMD patients and inflammatory cytokines. | IL-4,IL-10,IL-13, IFN-α, TGF-β, IL-1,IL-6, IL-17, IFN-β, IFN-γ and TNF-α | Through study completion，eight months. | 
| Correlation analysis between gut microbiota in MMD patients and neuroimaging markers and cognitive status. | MRI: BOLD, DWI, QSM, CUBE, ASL, T1, T2; Cognitive status: Wisdom, Attention, Memory, Linguistic fluency; | Through study completion，eight months. | 
| The differences of composition of gut microbiota among the genotypes (RNF213 p.R4810K) | RNF213 p.R4810K | Through study completion，eight months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moyamoya Disease, Microbiome, RNF213 p.R4810K, MRI