Molecular Mechanisms that Shape Gut Microbial Communities

塑造肠道微生物群落的分子机制

基本信息

批准号：
8415858
负责人：
Sarkis K Mazmanian
金额：
$ 39.57万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8415858
关键词：
Address Anatomy Animals Bacteria Bacteroides Bacteroides fragilis Base Sequence Biochemical Genetics Biological Process Biology Birth Cataloging Catalogs Communities Complex DNA Sequence Data Development Disease Disease model Ecology Ecosystem Evolution Fingerprint Funding Funding Opportunities Future Gastrointestinal tract structure Gene Deletion Genes Genetic Genetic Screening Genome Gnotobiotic Health Human Human Microbiome Immune system Intestines Investigation Laboratory culture Link Location Mammals Mediating Metagenomics Microbe Microscopic Molecular Mono-S Mucous Membrane Names Organism Pattern Population Positioning Attribute Process Research Project Grants Resistance Shapes Sterility Surface Symbiosis System Techniques Testing Therapeutic Tissues United States National Institutes of Health Virulence Factors Work base commensal microbes genetic manipulation gut microbiota human disease in vivo innovation member microbial microbial colonization microbial community microbial host microorganism mutant novel pathogen

项目摘要

DESCRIPTION (provided by applicant): Immediately upon a sterile birth, mammals assemble complex bacterial communities on almost all environmentally exposed surfaces (called the microbiota). Though it has been appreciated for decades that humans harbor multitudes of commensal bacteria, recent studies have begun to reveal the extraordinary diversity and complexity of our microbial ecosystems. The NIH funded Human Microbiome Project aims to define the "bacterial fingerprint" of humans in health and disease by cataloging DNA sequences of the microbiota. However, molecular mechanism(s) employed by commensal bacteria to mediate persistence in the gut remain almost entirely unknown. Bacteroides are one of the most numerically prominent and biologically important genera in the human microbiota. How these (or any other group of) bacteria stably colonize the mammalian gut is unknown. To understand the dynamics of host-microbiota associations in the gut, we developed a functional in vivo approach to identify mechanisms that mediate intestinal colonization. We identified a locus that encodes for a novel set of genes that are highly conserved in many sequenced intestinal Bacteroides. Most importantly, deletion of the genes abolishes stable colonization by Bacteroides. Collectively, our innovative findings strongly suggested we have uncovered a novel and evolutionarily conserved system for persistent gut colonization by the Bacteroides. Our overarching hypothesis is that a defined molecular mechanism mediates the dynamics of microbial ecology within the mammalian intestine.

描述（由申请人提供）：无菌出生后，哺乳动物几乎在所有环境暴露的表面（称为微生物群）上组装复杂的细菌群落。尽管几十年来，人类拥有许多共生细菌，但最近的研究开始揭示了我们微生物生态系统的非凡多样性和复杂性。 NIH资助的人类微生物组项目旨在通过将微生物群的DNA序列分类来定义人类在健康和疾病中的“细菌指纹”。然而，共生细菌用来介导肠道持续性的分子机制几乎完全未知。细菌是人类微生物群中数值最突出和生物学上最重要的属之一。这些（或其他任何其他）细菌如何稳定地定居于哺乳动物肠道。为了了解肠道中宿主 - 微生物群的动力学，我们开发了一种功能性的体内方法来识别介导脑定植的机制。我们确定了一个编码一组新型基因的基因座，这些基因在许多测序的肠道杀菌中都高度保守。最重要的是，这些基因的缺失消除了细菌的稳定定植。总体而言，我们的创新发现强烈表明，我们发现了一个新颖的，进化保守的系统，用于菌丝的持续肠道定植。我们的总体假设是，定义的分子机制介导了哺乳动物肠内微生物生态学的动力学。