Uncovering the modes and genetics of gut bacterial transmission

哺乳动物的肠道中有数百种细菌，这些细菌与它们的 宿主的新陈代谢、免疫和神经内分泌系统。在出生之前，哺乳动物缺乏明确的 肠道微生物区系，必须在每一代宿主中重新组装。个人获得 他们在出生时第一次从母亲那里接种疫苗，随后在一生中定居 由来自外部环境的细菌，包括社会接触。但是，这些模式由 哪些特定的肠道细菌谱系在宿主之间传播仍然知之甚少。它 目前还不清楚哪些肠道细菌谱系是忠实遗传的 哺乳动物多世代的宿主谱系。同样，相对贡献率 通过社交互动和共享环境进行的水平传播尚不清楚。 此外，细菌传播表型的潜在遗传基础尚未得到 被发现了。解决这些知识差距对于全面理解 补充哺乳动物谱系内遗传的遗传物质，共生进化 在肠道细菌和哺乳动物物种之间，肠道微生物区系的群落组装 在个别哺乳动物中，以及细菌肠道病原体在哺乳动物中的传播 人口。在这里，我们建议识别垂直和水平传输的成员 小鼠肠道微生物区系(目标1)及肠道细菌传播的遗传学基础 表型(目标2)。在目标1中，我们将采用一种创新的实验系统，利用 在室外围栏中饲养的野生来源的外交鼠种群，以解开这些模式 肠道微生物区系内的传播。作为这项工作的一部分，我们还将开发新的 从亚基因组组装高质量细菌基因组的方法将提供 研究细菌扩散的前所未有的机会。在目标2中，我们将使用转座子- 分散在无菌肠道内和之间的肠道细菌谱系的插入测序 在诺生菌隔离物中饲养的小鼠品系，以确定潜在的特定基因 肠道细菌传播表型。这项工作将集中在垂直和水平两个方面 我们以前的工作以及目标1的结果确定了传播的细菌谱系。 确定肠道细菌在哺乳动物内部和之间传播的遗传基础 谱系有可能重塑对糖尿病发病机制和进化的理解。 细菌扩散策略。此外，目标2将对发展作出重大贡献。 哺乳动物肠道细菌的功能基因组学工具。累积起来，拟议的工作将 对哺乳动物肠道细菌的传播方式有基本的见解。

Mammals harbor hundreds of bacterial species in the gut that are deeply integrated with their hosts’ metabolic, immune, and neuroendocrine systems. Before birth, mammals lack a defined gut microbiota, which must be assembled anew in each host generation. Individuals acquire their first inoculum from the mother during birth and are subsequently colonized throughout life by bacteria from the external environment, including social contacts. However, the modes by which specific gut bacterial lineages are transmitted between hosts remain poorly understood. It currently remains unknown which, if any, gut bacterial lineages are faithfully inherited within mammalian host lineages over multiple generations. Similarly, the relative contributions of horizontal transmission through social interactions and shared environments are unclear. Furthermore, the underlying genetic bases of bacterial transmission phenotypes have not been discovered. Resolving these knowledge gaps is of critical significance for understanding the full complement of genetic material inherited within mammalian lineages, the evolution of symbiosis between gut bacteria and mammalian species, the community assembly of the gut microbiota within individual mammals, and the spread of bacterial enteropathogens within mammalian populations. Here, we propose to identify vertically and horizontally transmitted members of the mouse gut microbiota (Aim 1) and to discover the genetic bases of gut bacterial transmission phenotypes (Aim 2). In Aim 1, we will employ an innovative experimental system that utilizes wild-derived outbred populations of mice reared in outdoor enclosures to disentangle the modes of transmission within the gut microbiota. As part of this work, we will also develop new approaches for assembling high-quality bacterial genomes from metagenomes that will provide unprecedented opportunities to study dispersal of bacteria. In Aim 2, we will employ transposon- insertion sequencing of gut bacterial lineages that disperse within and between germ-free mouse lines reared in gnotobiotic isolators in order to identify the specific genes that underlie gut bacterial transmission phenotypes. This work will focus on both vertically and horizontally transmitted bacterial lineages identified by our previous work as well as by results of Aim 1. Determining the genetic basis of gut bacterial transmission within and between mammalian lineages has the potential to reshape understanding of the mechanisms and evolution of bacterial dispersal strategies. In addition, Aim 2 will contribute substantially to the development of functional genomics tools in mammalian gut bacteria. Cumulatively, the proposed work will yield fundamental insights into the modes of gut bacterial transmission in mammals.