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，包含多达1000种不同的微生物物种。现在已知肠道内的微生物多样性影响人类健康和新陈代谢，并且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中取样的肠道微生物。这一目标可能对人类微生物组研究产生变革性影响，特别是是否存在“核心人类微生物组”的问题，这意味着所有健康人都共享微生物基因组多样性的某些方面。然而，迄今为止，几乎所有的研究都仅限于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破坏，并且可能从全球食物资源中引入微生物。拟议的研究是独特的，因为要研究的样本没有这种偏见。将使用最先进的基因组技术（包括新型基因阵列）分析样本。具体目标是（AIM 1）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，每个社区生活在三个非常不同的环境中：沿海沙漠，高海拔安第斯草原和亚马逊丛林。此外，还将包括一个古代社区，那里的样本是从木乃伊遗骸中提取的。AIM 2将使用下一代基因组测序和新型基因阵列技术表征这些样本中观察到的细菌菌种和细菌基因。AIM 3是分离微生物生态的关键成员。检验的假设包括：i）肠道微生物组具有地理结构，这意味着微生物分类群和基因功能的频率在种群内比种群之间更相似。ii）来自偏远社区的微生物群落具有高度的物种多样性。iii）在这些偏远的生态系统中存在新记录的微生物物种。㈣微生物在发达国家的肠道生态中是非典型的，在偏远社区中发挥着功能性作用。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逻辑贡献。 公共卫生相关性：人类微生物多样性被证明会影响人类疾病风险，药物代谢，并可能为新型药物治疗提供基础;然而，迄今为止，人类微生物多样性的范围在很大程度上限于工业化国家临床样本的观察。这项研究将极大地扩展人类微生物多样性的知识，通过使用最先进的技术来表征从生活在三个非常不同的环境中的当代偏远土著社区收集的人类肠道微生物：沿海沙漠，高海拔安第斯山脉和亚马逊丛林以及直接来自木乃伊化人类遗骸的古代样本。

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. PUBLIC HEALTH RELEVANCE: Human microbial diversity is shown to impact human disease risks, drug metabolism, and may provide a foundation for novel drug treatments; yet, to date, the range of human microbial diversity is largely limited to observations from clinical samples from industrialized nations. This study will greatly expand the knowledge of human microbial diversity by using state of the art technology to characterize human microbes of the gut collected from contemporary remote indigenous communities living in three very different environments: coastal desert, high altitude Andes, and the Amazon jungle as well as ancient samples derived directly from mummified human remains.