Characterizing the Genetic Determinants of Diverse Microbial Interactions in Two Dominant Bacterial Phyla of the Human Gut using Novel Experimental and Functional Genomic Approaches

 描述（由申请人提供）：人体肠道微生物群落是正常健康和发育的重要组成部分。结合宿主特异性因素，合作和竞争微生物相互作用的复杂网络塑造了这些社区的功能，多样性和结构。然而，这些相互作用的性质、机制和强度，以及它们施加的选择性压力，仍然难以量化。更好地了解肠道相关细菌如何相互作用，以及这些相互作用在不同生物系统发育和功能组中的分布程度，将为塑造人类肠道微生物群落的生态和进化力量提供有价值的见解。在这里，我们建议彻底映射竞争和合作的相互作用之间的两个占主导地位的肠道相关的细菌门的拟杆菌和厚壁菌门。我们将应用一种新的基于测序的方法来产生共培养物种的时间分辨定量，并通过使用全基因组转座子诱变文库来确定形成相互作用结果的遗传决定因素。通过这种方式，我们试图创建一个强大的机制框架，用于解释人类肠道中塑造微生物群落组装的生态过程和选择压力。这些是实现理解、诊断和治疗人类肠道微生物群落生态失调的最终目标的关键步骤。

 DESCRIPTION (provided by applicant): Microbial communities of the human gut are an essential component of normal health and development. In conjunction with host-specific factors, a complex network of cooperative and competitive microbial interactions shape the function, diversity, and structure of these communities. The nature, mechanism, and strength of these interactions, however, as well as the selective pressures they exert, remain difficult to quantify. A greater understanding of how gut-associated Bacteria interact, and the extent to which these interactions are distributed amongst different phylogenetic and functional groups of organisms, would provide valuable insight into the ecological and evolutionary forces shaping microbial communities of the human gut. Here we propose to thoroughly map competitive and cooperative interactions amongst two dominant gut-associated bacterial phyla-the Bacteroidetes and the Firmicutes. We will apply a novel sequencing-based approach to generate time-resolved quantification of co-cultured species and identify the genetic determinants shaping the outcome of interactions through the use of genome-wide transposon mutagenesis libraries. In this way, we seek to create a robust mechanistic framework for interpreting the ecological processes and selective pressures shaping microbial community assembly in the human gut. These are critical steps towards the ultimate goal of understanding, diagnosing, and treating dysbioses in human gut microbial communities.