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

人体肠道包含微生物（肠道微生物组），它们彼此之间以及与宿主之间存在复杂的相互作用。近年来对肠道微生物组多样性和组成的研究表明，肠道微生物组对营养、代谢和免疫反应有很大的影响。这些研究主要集中在工业化国家的城市人口，这些国家有更多的机会获得保健资源和富含高度加工食品的饮食。然而，对非工业化环境下的转基因知之甚少。在人类历史上，从狩猎和采集向农牧民和牧民的转变发生的时间相对较近（在过去的1万年内），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，这些人口在非洲大陆传播的过程中已经适应了一系列环境和食物，以了解转基因生物是如何与人类宿主和人类寄生虫共同进化的。这项研究将扩大对人类正常基因变异的了解，以及微生物组（包括工业化国家）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、当地社区外展、研究地点的教育和能力建设以及国际合作。本研究将通过表征转基因作物和土壤传播的蠕虫（STH）和血吸虫病（统称为蠕虫）寄生虫感染，在种族和地理上不同的非洲人口中进行一系列生存实践，评估有关人类适应和生物学的基本问题。将收集非洲牧民、农牧民和狩猎采集者的粪便样本、人种学数据和营养调查。定量PCR （qPCR）将用于检测几种常见蠕虫的粪便DNA，包括巨型蛔虫蛔虫和曼氏血吸虫。下一代16S核糖体细菌和古细菌DNA （16S rDNA）和真菌DNA的内部转录间隔区（ITS1）测序将表征转基因，并将对转基因成分和多样性与饮食、生存、地理、蠕虫的存在、缺失和丰度以及遗传祖先进行关联测试。这项研究扩大了对正常人类转基因变异谱的认识，以及寄生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主要疾病负担。该项目可以增加我们对蠕虫分布及其与转基因成分作为疾病发病机制潜在相关因素的关系的生物医学理解。

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.