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Impact of Diet on Intestinal Microbiota-Host Dynamics

饮食对肠道微生物群-宿主动态的影响

基本信息

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
项目类别：
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

项目摘要

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.