Doctoral Dissertation Research: Gut Microbiomes of Hunter-Gatherers: Roles of Diet and Helminths

人的肠道含有微生物(肠道微生物群)，它们彼此之间以及与人类宿主之间有着复杂的相互作用。最近对微生物组多样性和组成的研究表明，肠道微生物组(GM)对营养、代谢和免疫反应有很大的影响。这些研究主要侧重于工业化国家的城市人口，这些国家增加了获得卫生资源和富含精加工食品的饮食的机会。然而，人们对非工业化环境中的转基因知之甚少。在人类历史上，从狩猎和采集到农耕和畜牧业的转变发生在相对较近的时期(在过去10,000年内)，现代狩猎-采集者可能拥有新的转基因成分。该项目将研究非洲人口的转基因，他们在非洲大陆传播时已经适应了一系列环境和食物，以了解转基因是如何与其人类宿主和人类寄生虫共同进化的。这项研究将扩大关于转基因生物中正常人类变异的已知范围，以及微生物群(包括工业化世界中的微生物群)的差异如何影响健康。该项目将支持学生的教学和培训机会、当地社区推广、研究地点的教育和能力建设以及国际合作。这项研究将通过一系列生存实践，通过表征转基因生物和土传蠕虫(STH)和血吸虫病(统称为蠕虫)在种族和地理上不同的非洲人口中的寄生虫感染，来评估关于人类适应和生物学的基本问题。将从非洲牧民、农场主和狩猎采集者那里收集粪便样本、人种学数据和营养调查。定量聚合酶链式反应(QPCR)将用于检测几种常见蠕虫的粪便DNA，包括巨大蛔虫、蛔虫和曼氏血吸虫。下一代16S核糖体细菌和古菌DNA(16S RDNA)和真菌DNA的内部转录间隔区(ITS1)的测序将成为转基因的特征，并将对转基因成分和多样性与饮食、生存、地理、蠕虫的存在、缺失和丰富以及遗传祖先进行关联测试。这项研究扩大了人们对转基因正常人类变异范围的认识，以及蠕虫感染对转基因成分的影响。该项目对全球公共卫生也具有更广泛的意义，因为蠕虫感染是非洲的一项主要疾病负担。这个项目可以增加我们对蠕虫分布及其与GM成分的关系的生物医学理解，这些蠕虫是疾病发病机制中潜在的相关因素。

The human gut contains microorganisms (gut microbiome) that have complex interactions with one another and their human hosts. Recent research on microbiome diversity and composition has shown that the gut microbiome (GM) has a large influence on nutrition, metabolism, and immune response. These studies have focused primarily on urban populations from industrialized countries that have increased access to health resources and diets enriched in highly-processed food. However, less is known about the GM in non-industrialized settings. The shift from hunting and gathering to agriculturalist and pastoralist practices occurred relatively recent in human history (within the last 10,000 years), and modern hunter-gatherers may possess novel GM composition. This project will study the GM of African populations who have adapted to a range of environments and foods as they spread through the continent, to understand how GMs have co-evolved with their human hosts and with human parasites. The research will expand what is known about normal human variation in GMs, and how differences in the microbiome (including in the industrialized world) may influence health. The project will support teaching and training opportunities for students, local community outreach, education and capacity building at the study sites, and international collaborations.This research will assess fundamental questions about human adaptation and biology by characterizing GMs and soil-transmitted helminth (STH) and schistosomiasis (collectively referred to as helminths) parasite infections across ethnically and geographically diverse African populations with a range of subsistence practices. Fecal samples, ethnographic data, and nutrition surveys will be collected from African pastoralists, agriculturalists, and hunter-gatherers. Quantitative PCR (qPCR) will be used to test fecal DNA for several common species of helminths, including the giant roundworm Ascaris lumbricoides and fluke Schistosoma mansoni. Next-generation sequencing of 16S ribosomal bacterial and archaeal DNA (16S rDNA) and internal transcribed spacer (ITS1) region of fungal DNA will characterize GMs, and association testing will be done on GM composition and diversity with diet, subsistence, geography, presence, absence, and abundance of helminths, and genetic ancestry. The research expands knowledge of the spectrum of normal human variation in GM and the impact of helminth infection on GM composition. This project is also of broader significance for global public health since helminth infection is a major disease burden in Africa. This project can increase our biomedical understanding of the distribution of helminths and their relationships with GM composition as potentially correlated factors in the pathogenesis of disease.