Genetic Transmission of Componenets of the Human Gut Microbiome

人类肠道微生物组成分的遗传传递

• 批准号: 9447889
• 负责人: ANDREW G CLARK
• 金额: $ 45.39万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9447889
• 关键词: Adult; Affect; Architecture; Area; Bacteria; Biological; Biology; Blood; Chronic; Communities; Computing Methodologies; Culture Techniques; Data; Data Set; Development; Diabetes Mellitus; Diet; Disease; Dissection; Drug usage; Environmental Impact; Exercise; Factor V; Filtration; Food; Frequencies; Funding; Genealogy; Genes; Genetic; Genetic Determinism; Genetic Variation; Genome; Genotype; Gnotobiotic; Goals; Growth; Hand; Haplotypes; Health; Heritability; Hour; Human; Human Genome; Human body; Individual; Inflammatory; Knowledge; Life Style; Link; Mass Spectrum Analysis; Measures; Mediating; Metabolic; Metabolic Pathway; Metagenomics; Methods; Microbe; Monozygotic twins; Mus; Mutation; Nucleotides; Obesity; Organism; Pathway interactions; Phenotype; Physiological; Physiology; Play; Predisposition; Prevention; Prevotella; Property; Public Health; Questionnaires; Research; Resolution; Resources; Ribosomal RNA; Role; SNP genotyping; Sampling; Series; Shotguns; Smoking; Specificity; Structure; Surveys; System; Taxonomy; Testing; Thinness; Time; Twin Multiple Birth; Variant; Volatile Fatty Acids; Whole Organism; aged; cohort; fecal transplantation; genetic association; genome wide association study; genome-wide analysis; gut microbiome; host-microbe interactions; improved; indexing; metabolomics; metagenome; metagenomic sequencing; microbial; microbiome; mouse model; novel; obesity risk; personalized medicine; therapy design; transmission process; whole genome

Project Summary The microbes that inhabit the human body are viewed as an integral component of our biology, and microbiome variability has been found to result in differences in disease predisposition. The proposed research will develop and apply methods to infer how variation in the human genome mediates composition and function of the gut microbiome. To achieve this objective, we will pursue four specific aims in an analysis of genome-wide SNP genotype data already available from the TwinsUK project to identify genetic determinants of microbiome composition. For Specific Aim 1, we will use whole- genome sequence data of the twins along with deep metagenomic sequencing of their gut microbiomes to infer heritability and gene-specific associations with a) greater resolution taxonomic data, and b) metabolic attributes of the bacterial community. These data are already in hand, and provide unique opportunities to dissect the means by which variation in the human genome mediates gut microbiome properties. For Specific Aim 2, we will infer individual strains in the gut microbiomes from the metagenomics data, making use of the fact that our sequencing depth is sufficient to identify clonal haplotypes of the most common ~50 bacterial species. The biological impacts of specific strains can vary widely, and this strain-specific analysis is likely to be highly informative by improving specificity and accuracy of associations between host genes and microbiome composition. For Specific Aim 3, we will resample 1000 individuals from the original TwinsUK microbiome survey, and use this information to identify attributes of the gut microbiome that are stable over time, and to test the relationship between heritability and stability of microbes in the microbiome. For Specific Aim 4, we will use the gnotobiotic mouse experimental system to dissect the effects of the heritable bacterium Christensenella minuta on gut function as well has whole-organism physiology. The results of this research will be used to establish links between regions of the human genome and composition of the microbiome. The results of this study have the potential to reveal fundamental human host-microbe interactions that may be applicable to the prevention and treatment of chronic inflammatory diseases.

项目摘要 居住在人体内的微生物被视为我们生物学的组成部分， 已经发现微生物组变异性导致疾病易感性的差异。拟议 研究将开发和应用方法来推断人类基因组中的变异如何介导 肠道微生物组的组成和功能。为达致这个目标，我们会推行四项具体措施， 目的是分析TwinsUK项目已经提供的全基因组SNP基因型数据， 确定微生物组组成的遗传决定因素。对于具体目标1，我们将使用整个- 双胞胎的基因组序列数据沿着以及他们肠道的深层宏基因组测序 微生物组推断遗传性和基因特异性关联a）更高分辨率的分类 数据，和B）细菌群落的代谢属性。这些数据已经掌握，并提供 独特的机会来剖析人类基因组中的变异介导肠道的方式， 微生物组特性。对于特定目标2，我们将推断肠道微生物组中的单个菌株 从宏基因组学数据中，利用我们的测序深度足以识别 最常见的~50种细菌的克隆单倍型。特定菌株的生物学影响 可以有很大的差异，这种菌株特异性分析可能通过提高特异性而提供高度信息 以及宿主基因和微生物组组成之间关联的准确性。具体目标3： 将从最初的TwinsUK微生物组调查中重新取样1000人，并使用 信息，以确定随时间推移稳定的肠道微生物组的属性，并测试 微生物组中微生物的遗传性和稳定性之间的关系。具体目标4： 利用知菌小鼠实验系统解剖遗传菌的作用， 微小克里斯滕森氏菌对肠道功能的影响也具有整体生理学意义。的结果 研究将用于建立人类基因组区域与基因组组成之间的联系。 微生物组本研究的结果有可能揭示人类宿主微生物的基本原理 这些相互作用可能适用于预防和治疗慢性炎性疾病。