Defining and Reconstructing the Human Ancestral Microbiome

定义和重建人类祖先微生物组

• 批准号: 10221605
• 负责人: JUSTIN L SONNENBURG
• 金额: $ 109.9万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221605
• 关键词: Address; Affect; Archives; Biological; Biology; Chronic Disease; Collection; Complement; Complex; Disease; Distal; Environment; Gastrointestinal tract structure; Generations; Genes; Gnotobiotic; Goals; Health; Human; Human Biology; Human Genome; Human Microbiome; Immunotherapy; Industrialization; Inflammatory; Knowledge; Life Style; Modernization; Molecular Genetics; Population; Public Health; Research; Shapes; Therapeutic; Translating; gut microbiota; human microbiota; improved; insight; metagenomic sequencing; microbial; microbial community; microbiome; microbiota; mouse model; novel; prevent; stool sample; tool; vaccine efficacy

The gut microbiota is an integrated part of human biology and has coevolved with us, passing from generation to generation for millions of years. Therefore, the species that are likely to have biology most compatible with the human genome are specific and not a random collection that we can assemble from the surrounding environment and let the prevailing selective forces shape. The plasticity of the gut microbiota offers tremendous potential for therapeutic manipulation, but this malleability can translate into species-loss during perturbations like those that have accompanied industrialization. The microbiota of people living a Western lifestyle differs substantially from that of traditional populations whose lifestyles are relatively free of the forces of modernization. These “traditional” microbiotas contain taxa that are common to traditional populations on different continents yet are absent or exceedingly rare among people in the industrialized world. This project aims to understand the species and genes that define and differentiate the microbiome of traditional populations. A primary goal of this research is to pursue a deep biological understanding of how compositional and functional differences between the traditional microbiota and Western microbiota affect human biology. Using existing de-identified archived stool samples from hunter-gatherers, a variety of tools will be applied including deep metagenomic sequencing, isolation and characterization of microbial species that are absent or rare in the Western gut, gnotobiotic mouse models, and molecular genetics. This study will result in an important, novel understanding of the human microbiome, one that addresses the fundamental question of what defines the microbiomes that our species evolved with. Investigating the microbiome from an evolutionary perspective will yield insight into how missing components of our biology may be complemented via gut microbiota colonization. This approach will significantly contribute to preventing and treating a spectrum of non-communicable chronic diseases.

肠道微生物区系是人类生物学中不可或缺的一部分，并与我们共同进化，代代相传。 几百万年来的世代。因此，最有可能在生物学上与人类最相容的物种 基因组是特定的，而不是我们可以从周围环境中组装起来的随机集合 占主导地位的选择性力量塑造了。肠道微生物区系的可塑性为治疗提供了巨大的潜力 操纵，但这种延展性可以转化为物种在扰动期间的损失，如伴随着 工业化。西方生活方式的人的微生物区系与传统的生活方式有很大不同 生活方式相对不受现代化力量影响的人群。这些“传统的”微生物群包含 在不同大陆的传统种群中常见的分类群，但在中国人中缺乏或极其罕见 工业化世界。这个项目旨在了解定义和区分生物的物种和基因 传统种群的微生物群。这项研究的一个主要目标是寻求深入的生物学理解 传统微生物区系与西方微生物区系在组成和功能上的差异影响人类 生物学。利用现有的来自狩猎-采集者的未确认的存档粪便样本，将应用各种工具 包括深层元基因组测序，分离和鉴定在世界上不存在或罕见的微生物物种 西方肠道、诺生菌小鼠模型和分子遗传学。这项研究将产生一项重要的、新颖的 对人类微生物组的理解，解决了定义微生物组的根本问题 我们的物种与之共同进化。从进化的角度研究微生物组将使我们深入了解 我们生物学中缺失的部分可以通过肠道微生物区系定植来补充。这一方法将 为预防和治疗一系列非传染性慢性病作出重大贡献。