Human Intestinal Microbial Ecologies of Indigenous Communities

描述（由申请人提供）：人类肠道是一个复杂的生态系统，拥有多达1000种不同的微生物物种。现在我们知道肠道内的微生物多样性影响着人类的健康和新陈代谢，人们希望对人类微生物多样性的研究将导致新的医学治疗。本研究的目的是表征从生活在偏远地理区域的人取样的肠道微生物。这一目标可以对人类微生物组研究产生变革性影响，特别是是否存在一个“核心人类微生物组”的问题，即所有健康人共享的微生物基因组多样性的某些方面。然而，迄今为止，几乎所有的研究都局限于来自发达国家的临床样本。这些样本具有确定偏差，因为人类微生物组多样性的自然状态被抗生素等药物以及可能从全球食物资源引入的微生物所破坏。所提出的研究的独特之处在于所研究的样本缺乏这种偏差。样品将使用最先进的基因组技术进行分析，包括一种新的基因阵列。具体目标是（AIM1）从三个偏远的当代秘鲁土著社区收集粪便样本并记录饮食信息，每个社区都生活在三种截然不同的环境中：沿海沙漠、高海拔安第斯草原和亚马逊丛林。此外，还将包括一个从木乃伊遗骸中提取样本的古代社区。AIM2是利用下一代基因组测序和新型基因阵列技术对这些样品中观察到的细菌种类和细菌基因进行表征。AIM3是分离微生物生态的关键成员。经检验的假设包括：1)肠道微生物组具有地理结构，这意味着同一种群内微生物类群的频率和基因功能比种群间更相似。Ii)来自偏远群落的微生物组具有较高的物种多样性。Iii)在这些偏远的生态系统中存在新记录的微生物区系物种。Iv)微生物，在发达国家的非典型肠道生态中，在偏远社区中发挥功能作用。这些假设中的每一个都是对评估人类微生物多样性和核心人类微生物组存在程度的合理贡献。

DESCRIPTION (provided by applicant): The human gut is a complex ecosystem harboring up to a 1000 different microbial species. It is now known that microbial diversity within the gut impacts human health and metabolism and it is hoped that the study of human microbial diversity will lead to novel medical treatments. The objective of this study is to characterize gut microbes sampled from people living in remote geographic areas. This objective can have a transformative impact on human microbiome research, especially the question of whether there is a "core human microbiome", meaning, some aspect of microbial genome diversity that all healthy people share. Yet, nearly all studies to date are limited to clinical samples from developed nations. These samples have an ascertainment bias because the natural state of human microbiome diversity is disrupted by medications such as antibiotics, and likely, introductions of microbes from global food resources. The proposed study is unique in that the samples to be studied lack this bias. Samples are to be analyzed using state of the art genome technologies, including a novel gene array. The specific aims are (AIM1) to collect fecal samples and record dietary information from three remote contemporary native Peruvian communities, each living in three very different environments: coastal desert, high-elevation Andean grasslands, and the Amazon jungle. In addition, one ancient community, where samples were retrieved from mummified remains, will be included. AIM2 is to characterize the bacterial species and bacterial genes observed in these samples using next generation genome sequencing and novel gene array technologies. AIM3 is to isolate key members of the microbial ecology. Hypotheses tested include: i) gut microbiomes are geographically structured, meaning the frequencies of microbial taxa and gene functions are more similar within a population than between populations. ii) microbiomes from remote communities have high species diversity. iii) newly recorded species of microflora are present within these remote ecologies. iv) microbes, atypical of gut ecologies in developed nations, assume functional roles within remote communities. Each of these hypotheses is a logical contribution to assessing human microbial diversity and the extent to which a core human microbiome exists.