Impact of Diet on Intestinal Microbiota-Host Dynamics

饮食对肠道微生物群-宿主动态的影响

• 批准号: 9313246
• 负责人: JUSTIN L SONNENBURG
• 金额: $ 39.5万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-07 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9313246
• 关键词: Address; Biological; Carbohydrates; Colon Carcinoma; Communities; Complex; Data; Developed Countries; Diet; Diet Modification; Dietary Component; Dietary Fiber; Dietary Intervention; Dietary Supplementation; Disease; Eating; Ecosystem; Elements; Extinction (Psychology); Feces; Fermentation; Fiber; Food; Funding; Gastrointestinal tract structure; Generations; Genes; Goals; Grant; Health; Human; Human Biology; Immigration; Individual; Industrialization; Inflammation; Inflammatory Bowel Diseases; Intake; Intervention; Intestines; Kinetics; Lead; Link; Metabolic; Metabolic Marker; Metabolic syndrome; Metabolism; Metagenomics; Methods; Microbe; Modernization; Monitor; Mus; Nutrient; Obesity; Output; Persons; Plague; Plants; Play; Polysaccharides; Process; Research Project Grants; Ribosomal RNA; Role; Shapes; Societies; Supplementation; Surveys; Testing; Time; Transplantation; Volatile Fatty Acids; Western World; absorption; experience; gut microbiota; humanized mouse; improved; member; metabolomics; metagenomic sequencing; microbial; microbial community; microbiota; microbiota transplantation; public health relevance; small molecule

 DESCRIPTION (provided by applicant): The human gut harbors a dense and complex community of microbes known as the intestinal microbiota. This microbial ecosystem is connected to many facets of human biology in health, but can also contribute to several diseases including inflammatory bowel diseases, obesity, and colon cancer. Diet is a major determinant of both the microbial species, or phylotypes, that inhabit one's microbiota, as well as the functions carried out by these species. Specifically, dietary microbiota-accessible carbohydrates (MACs), the main component of dietary fiber, serve as the primary metabolic input for the gut microbiota. Modern diets have significantly less dietary fiber relative to those from traditional societies, an observation that has been linked to the decrease in microbiota diversity (e.g., less microbial species) in individuals from industrialized countries. Low diversit microbiotas, in turn, have been correlated with markers of metabolic syndrome and inflammation, and increased dietary fiber appears to improve microbiota diversity and health. Yet large gaps still exist in understanding how dietary MACs influence microbiota diversity and whether dietary MAC depletion can result in irreversible loss of phylotypes within the microbiota. This proposal aims to define the influence of dietary MACs on microbiota diversity and microbial metabolism and to determine how extinct microbial phylotypes can be successfully reintroduced into low diversity communities. In Aim 1, mice harboring a human microbiota (`humanized') eating defined diets will be used to determine the major consequences that restricting dietary MACs has on metabolites, genes, and species within the gut. To determine whether a diet- induced reduction in microbiota diversity can be reversed upon re-introduction of MACs, mice will be deprived of MACs, followed by reintroduction of MACs, and their microbiota composition and function will be defined. The effect of MAC depletion over multiple generations on diversity loss will also be determined. Microbiota functionality will be assessed by metagenomic, short-chain fatty acid, and metabolomic analyses. In Aim 2, the microbiota of humans undergoing a dietary intervention with fiber supplements will be assessed. Alterations in microbiota composition and functionality will be compared using fiber supplements that vary in structural complexity. Gene content and small molecule metabolites will be similarly defined using metagenomic, short-chain fatty acid, and metabolomic analyses. The goal of Aim 3 is to identify the best method to introduce bacterial phylotypes to restore diversity into humanized mice that harbor a low diversity microbiota. Microbiota reprogramming strategies include transplanting (i) an intact microbiota from a high- diversity donor, (ii) a complex culturable microbiota from high-diversity stool, or (iii) defined communities composed of culturable type strains. Successful strategies, defined as those that significantly increase microbiota diversity, will be tracked over time to determine the kinetics of new strain establishment.

 描述（通过应用程序证明）：人类的肠道浓密的微生物（称为肠道微生物）的密集anse anse anse anse com nse anse comential come comecystin in the Iltestinal sirobita。肥胖症和结肠癌是微生物物种的主要决定因素，或者是居住在这些物种中的一种微生物群体的饮食中。肠道微生物的主要代谢性饮食中的MAC耗竭是否会导致该提案的不可逆损失，以定义微生物的饮食型MACR。人类微生物群（“人性化”）饮食饮食遗嘱，以确定肠内饮食中的饮食中的饮食中的饮食中的Mac，以确定在Mac的重新介绍的饮食中的饮食中的饮食中的多样性。 ，将剥夺MAC，然后将MAC罚款的MAC对多代对多样性损失的影响也将通过元基因组损失。人类的微生物群体将使用微生物群体组成。 AL AL 3是为了将多样性的微生物群从高多样性粪便或（III）定义的社区中，将多样化的小鼠恢复到人性化的小鼠中这是明显的indrobiota多样性，将跟踪 是时候确定新应变建立的动力学了。