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.

肠道微生物群是人类生物学的一个组成部分，与我们共同进化，代代相传。 数百万年的一代。因此，生物学上最可能与人类相容的物种 基因组是特定的，而不是我们可以从周围环境中组装的随机集合， 主导选择力的形状。肠道微生物群的可塑性为治疗提供了巨大的潜力。 操纵，但这种可塑性可以转化为物种损失在扰动，如那些伴随着 产业化生活在西方生活方式中的人的微生物群与传统生活方式有很大不同。 生活方式相对不受现代化影响的人口。这些“传统”微生物含有 分类群是共同的传统人群在不同的大陆，但缺席或极为罕见的人， 工业化世界。该项目旨在了解定义和区分生物的物种和基因， 传统人群的微生物。这项研究的一个主要目标是追求一个深刻的生物学理解， 传统微生物群和西方微生物群之间的组成和功能差异影响人类 生物学使用现有的去识别存档粪便样本从狩猎采集，各种工具将被应用 包括深度宏基因组测序，分离和表征在微生物中不存在或罕见的微生物物种， 西方肠道，gnotobiotic小鼠模型和分子遗传学。这项研究将产生一个重要的，新颖的 对人类微生物组的理解，解决了什么定义微生物组的基本问题 我们物种的进化方式从进化的角度调查微生物组将深入了解如何 我们生物学中缺失的成分可以通过肠道微生物群的定植来补充。这种方法将 这将大大有助于预防和治疗一系列非传染性慢性疾病。