Molecular Mechanisms that Shape Gut Microbial Communities

描述（由申请人提供）：在无菌分娩后，哺乳动物在几乎所有暴露于环境的表面上聚集复杂的细菌群落（称为微生物群）。虽然几十年来人们一直认为人类体内有大量的共生细菌，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群的DNA序列进行编目，确定人类健康和疾病的“细菌指纹”。然而，共生菌介导肠道内持久性的分子机制仍然几乎完全未知。拟杆菌是人类微生物群中数量最多、生物学上最重要的属之一。这些（或其他任何一组）细菌是如何在哺乳动物的肠道中稳定地定植的尚不清楚。为了了解肠道中宿主-微生物群关联的动力学，我们开发了一种功能体内方法来确定介导肠道定植的机制。我们发现了一个位点，它编码一组新的基因，这些基因在许多已测序的肠道拟杆菌中高度保守。最重要的是，基因的缺失使拟杆菌的稳定定植消失。总的来说，我们的创新发现强烈表明，我们已经发现了一种新的、进化上保守的系统，用于拟杆菌的持续肠道定植。我们的首要假设是，一个明确的分子机制介导了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.