Defining and Reconstructing the Human Ancestral Microbiome

定义和重建人类祖先微生物组

• 批准号: 9980347
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980347
• 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。 世代传承了数百万年。因此，可能具有与人类最相容的生物学特性的物种 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，并让 普遍存在的选择性力量的形成。肠道微生物群的可塑性为治疗提供了巨大的潜力 操纵，但这种可塑性可能会在扰动期间转化为物种丧失，就像那些伴随而来的扰动一样 工业化。西方生活方式的人的微生物群与传统生活方式的人有很大不同 生活方式相对不受现代化影响的人群。这些“传统”微生物群含有 不同大陆的传统人群所共有的类群，但在不同大陆的人群中不存在或极其罕见 工业化世界。该项目旨在了解定义和区分物种的物种和基因 传统人群的微生物组。这项研究的主要目标是深入了解如何 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着人类 生物学。使用来自狩猎采集者的现有去识别化存档粪便样本，将应用各种工具 包括深度宏基因组测序、微生物物种的分离和表征，这些微生物物种在自然界中不存在或罕见。 西方肠道、限生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 了解人类微生物组，解决微生物组定义的基本问题 我们的物种随之进化。从进化的角度研究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定植来补充。这种方法将 为预防和治疗一系列非传染性慢性疾病做出了重大贡献。