Impact of the Intestinal Microbiota on the Host Epigenome and Obesity Phenotype

肠道微生物群对宿主表观基因组和肥胖表型的影响

• 批准号: 9059130
• 负责人: Amanda Ellen Ramer-Tait
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9059130
• 关键词: Adipose tissue; Affect; Architecture; Asthma; Bacteria; Bioinformatics; Biomedical Research; Biostatistics Core; CD4 Positive T Lymphocytes; Cells; Centers of Research Excellence; Cesarean section; Childhood; Choline; Chronic; Data; Data Set; Development; Diet; Dietary Intervention; Disease; Employee Strikes; Environmental Risk Factor; Epigenetic Process; Event; Exposure to; Future; Gastrointestinal tract structure; Genes; Genome; Goals; Health; High Fat Diet; High-Throughput Nucleotide Sequencing; Homeostasis; Human; Immune; Immune system; Immunology; Individual; Inflammation; Inflammatory; Intestinal Mucosa; Intestines; Lead; Life; Lipids; Liver; Lung; Mammalian Cell; Maps; Mediating; Mentors; Metabolic; Metabolic Diseases; Microbe; Microbiology; Molecular; Molecular Biology; Molecular Weight; Mus; Nebraska; Nutrient; Obesity; Organism; Outcome; Peripheral; Phenotype; Positioning Attribute; Regulation; Repression; Research Infrastructure; Role; Scientist; Sclerosis; Sequence Analysis; Signal Transduction; Spleen; Staging; T-Lymphocyte; Technology; Testing; Training; Universities; Work; adaptive immunity; design; epigenome; feeding; gastrointestinal; genome sequencing; gut microbiota; imprint; microbial; microbial colonization; microbial host; microbiota; mouse model; novel; obesity prevention; pathogen; prevent; transcription factor

The human gastrointestinal tract is populated with as many as 100 trillion bacteria that provide their host with dietary metabolites and protecfion against pathogens. Increasing evidence indicates appropriate intestinal microbiota colonization during early stages of life is important for preventing immune-mediated diseases later in life. A key question is: How does the early intestinal microbiota provide these long-term benefits? Evidence is emerging that the human gut microbiota participates in the creation of epigenetic marks, thereby impacfing long-term gene regulafion with consequences for health. The intestinal microbiota has also been implicated in obesity, a chronic inflammatory condifion now associated with eariy life events affecfing assembly of the gut microbiota, including cesarean secfions, anfibiofics, and formula feeding. These observafions suggest that disrupfion of the early gut microbiota may lead to metabolic deficiencies later in life through epigenetic mechanisms; however, the specific microbiotaregulated targets that influence the obese phenotype are currently unknown. Dr. Ramer-Tait will test the hypothesis that the lack of symbiotic microbiota during eariy development precipitates regulation of proinflammatory T cell phenotype genes via epigenetic mechanisms, with long-term consequences for metabolic health. She will combine gnotobiofic mouse models with high-throughput sequencing technologies to study the interacfions among the microbiota, the immune system, and the epigenome in the context of obesity. During her project. Dr. Ramer-Tait will employ her extensive training in immunology, microbiology, and gnotobiofic mouse models of inflammatory diseases. Her COBRE mentors include a well-respected molecular microbial ecologist with expertise in high throughput sequence analyses and a bioinformatician with vast expertise in analysis of large data sets derived from genome sequencing projects. This project will advance the thematic focus of the associated proposed Nebraska Center for the Prevention of Obesity Disease through Dietary Molecules by providing critical information about how the gut microbiota regulates the host immune system and precipitates metabolic diseases. By understanding these host-microbial relafionships, we can strategically design novel dietary interventions to control obesity by modulafing the intestinal microbiota.

人类胃肠道有多达100万亿个细菌，可提供其宿主 饮食代谢产物和针对病原体的蛋白质。越来越多的证据表明适当 生命早期肠道菌群定植对于预防免疫介导的 以后的疾病。一个关键问题是：早期肠道菌群如何提供这些长期 好处？有证据表明人类肠道菌群参与表观遗传的创造 标记，从而使长期基因调节造成了对健康的影响。肠道 微生物群也与肥胖有关，这是一种与现在有关 肠道微生物群（包括剖宫产，Anfibiofics和 配方奶粉。这些观察结果表明，早期肠道菌群的解散可能导致 生命之后的代谢缺陷通过表观遗传机制；但是，特定的微生物处理 影响肥胖表型的目标目前尚不清楚。 Ramer-Tait博士将测试 假设在耳过程中缺乏共生微生物群会导致促炎性的调节 T细胞表型基因通过表观遗传机制，对 代谢健康。她将将gnotobiofic小鼠模型与高通量测序相结合 研究微生物群，免疫系统和表观基因组之间的间隔的技术 肥胖的背景。在她的项目中。拉默·泰特（Ramer-Tait）博士将接受她的广泛培训 炎症性疾病的免疫学，微生物学和gnotobiofic小鼠模型。她的毛绒 导师包括一个受尊敬的分子微生物生态学家，具有高吞吐量的专业知识 序列分析和具有丰富专业知识的生物信息学家，分析了来自 基因组测序项目。该项目将推进相关提议的主题重点 内布拉斯加州通过饮食分子预防肥胖疾病的中心通过提供关键 有关肠道微生物群如何调节宿主免疫系统并沉淀代谢的信息 疾病。通过了解这些宿主微生物的遗产，我们可以战略性地设计新颖的饮食 通过调节肠道菌群来控制肥胖的干预措施。