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The Interplay of Host Genetic Variation and the Gut Microbiome in Crohn's Disease

克罗恩病宿主遗传变异与肠道微生物组的相互作用

基本信息

批准号：
10751276
负责人：
Shreya Nirmalan
金额：
$ 4.74万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-17 至 2027-08-16
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10751276
关键词：
Affect Alleles Allelic Imbalance Architecture Autoimmune Diseases Binomial Model Caring Chemicals Chronic Cicatrix Coculture Techniques Communities Complex Computational Biology Computing Methodologies Crohn&apos s disease Data Databases Diet Digestive System Disorders Disease Environmental Risk Factor Functional disorder Gastrointestinal tract structure Gene Expression Gene Modified Genes Genetic Genetic Risk Genetic Transcription Genetic Variation Genomic approach Genotype Human Human Microbiome Immune Immune response Immunosuppressive Agents Individual Inflammation Inflammatory Inflammatory Bowel Diseases Intestines Maps Metabolic Methods Microbe Morbidity - disease rate Newly Diagnosed Operative Surgical Procedures Opioid Organoids Outcome Pathogenesis Pathologic Patient Isolation Patients Persons Pharmaceutical Preparations Phenotype Physiological Quality of life Regulator Genes Research Route Shotguns Stimulus Taxonomy Testing Treatment Cost Variant cost differential expression disability disorder risk dysbiosis experience functional genomics genetic risk factor genetic variant genome wide association study gut microbiome host microbiome host-microbe interactions insight metagenomic sequencing microbial microbial community microbial composition microbiome microbiome composition microbiota microorganism new therapeutic target novel novel therapeutics pathogen personalized therapeutic response risk variant therapeutic target transcriptome transcriptome sequencing

项目摘要

ABSTRACT Crohn’s Disease (CD) is an autoimmune disease which leads to chronic inflammation and scarring of the digestive tract. The available treatments involve immunosuppressants and surgery which are costly, with many individuals still experiencing a decreased quality of life. The cause of CD is unknown, but is believed to occur due to both genetic and environmental factors, including diet. The gut microbiome is altered in individuals with CD, leading to dysregulation of the host and microbial transcriptional and metabolic landscape. Furthermore, many genetic risk variants associated with CD are in host genes known to function in host response to the microbiome. Thus, characterizing host-microbiome interactions in CD is imperative for understanding the pathogenesis of CD and identifying potential new therapeutic routes. In this proposed research, I aim to characterize the interactions between host genetic variation and the gut microbiome that regulate host gene expression in CD. I will use two complementary approaches. I will use a microbiome/intestinal organoids co-culturing approach to identify host gene expression changes in response to CD-derived microbiomes, and host genetic variants that modulate these changes using allele-specific expression analysis. I will also utilize data available through the Human Microbiome Project Inflammatory Bowel Disease Multi’omics Database to perform eQTL mapping, and integrate all of my findings with GWAS and TWAS to validate the significance of GxM for CD risk. These studies will provide insight into host-microbiome interactions that modify genetic risk for Crohn’s Disease. Furthermore, I will identify specific microbes that could become potential therapeutic targets for CD.

摘要