Molecular Mechanisms that Shape Gut Microbial Communities

描述(申请人提供)：在无菌分娩后，哺乳动物立即在几乎所有暴露在环境中的表面(称为微生物区系)上聚集复杂的细菌群落。尽管几十年来人们一直意识到人类拥有大量的共生细菌，但最近的研究已经开始揭示我们微生物生态系统的非凡多样性和复杂性。美国国立卫生研究院资助的人类微生物组项目旨在通过对微生物区系的DNA序列进行编目，定义人类在健康和疾病中的“细菌指纹”。然而，共生细菌调节肠道持久性的分子机制(S)几乎完全不清楚。类杆菌是人类微生物区系中数量最多、生物学意义最重要的属之一。这些(或其他任何一组)细菌如何稳定地在哺乳动物的肠道中定居尚不清楚。为了了解肠道中宿主-微生物区系联合的动态，我们开发了一种体内功能方法来确定介导肠道定植的机制。我们确定了一个编码一组新基因的基因座，这些基因在许多已测序的肠道类杆菌中高度保守。最重要的是，基因的缺失会取消类杆菌的稳定定植。总而言之，我们的创新发现有力地表明，我们已经发现了一种新颖的、进化上保守的系统，用于由类杆菌持续的肠道定植。我们的主要假设是，一个明确的分子机制调节哺乳动物肠道内微生物生态的动态。

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.