Adaptation to diet and its impact on the gut microbiome and genomic variation

全球各地的饮食差异很大，我们消化食物的能力取决于人类基因组中存在的基因和人类肠道中发现的细菌（即肠道微生物群）。在过去的几年里，科学家们发现肠道微生物组对人体生理有非常重要的影响，可以影响营养状况，以及疾病风险。事实上，肠道微生物组的变异被认为在肥胖、营养不良、自身免疫性疾病和传染病易感性中发挥作用。然而，我们不知道肠道细菌在不同人群中的差异有多大，以及这种差异的原因是什么。此外，与消化、营养和免疫有关的人类基因存在大量差异，特别是在非洲人群中。通过关注种族和地理上多样化的非洲人实践各种人类饮食，该研究项目可以极大地有助于理解我们物种生物学的这些基本重要方面，解决有关现代人类历史和与人类生物学和适应相关的特征的遗传基础的基本问题。该研究将包括对非洲东部、中部和南部三个狩猎采集人群、三个游牧人群和三个农业人群的实地研究。收集的数据将包括人体测量数据（例如身高、体重和体重）、不同非洲人的DNA序列、乳糖耐受性数据、饮食和营养的详细信息以及粪便样本（这将允许评估肠道微生物群中存在的细菌）。肠道微生物组数据将与有关营养的详细信息以及人体测量学、代谢和遗传数据相结合，以更好地了解有助于人类适应饮食的遗传和环境因素。例如，饮用大量牛奶的牧民的肠道细菌可能被富集为能够代谢牛奶中存在的乳糖的物种，因此，可能为研究导致乳糖耐受性的因素以及在更大范围内理解基因、培养和细菌共同适应提供信息。该项目将对人类学、遗传学、微生物学和进化生物学等领域做出重大贡献。鉴于与其他地理区域相比，我们对非洲遗传和表型多样性的认识存在差距，这项研究产生的可公开获得的数据将成为人类学家、微生物学家和遗传研究人员的重要资源，有助于研究人类起源以及设计和解释疾病关联研究。此外，由于肠道微生物组对营养、代谢和免疫反应有很大影响，因此该研究项目可能对了解糖尿病、传染病和营养不良的危险因素产生重要影响。通过合作研究，该项目还将对美国和非洲学生和科学家的研究培训作出重大贡献。

Diets vary greatly across the globe, and our ability to digest foods depends on genes present in the human genome and bacteria found in the human gut (i.e., the gut microbiome). Within the past few years, scientists have discovered that the gut microbiome has a very important influence on human physiology and can impact nutritional status, as well as disease risk. Indeed, variation in the gut micriobiome is thought to play a role in obesity, malnutrition, auto-immune disease, and infectious disease susceptibility. However, we do not know how much gut bacteria vary across diverse human populations, and what may account for that variation. In addition, substantial variation exists for human genes involved in digestion, nutrition, and immunity, particularly for African populations. By focusing on ethnically and geographically diverse Africans practicing a variety of human diets, this research project can significantly contribute to understanding these fundamentally important aspects of the biology of our species, addressing fundamental questions about modern human history and the genetic basis of traits related to human biology and adaptation.The research will include field studies of three hunter-gather, three pastoralist, and three agriculturalist populations in Eastern, Central, and Southern Africa. Data collected will include anthropometric measurements (e.g. height, weight, and body mass), DNA sequences of diverse Africans, lactose tolerance data, detailed information about diet and nutrition, and fecal samples (which will allow assessment of bacteria present in the gut microbiome). The gut microbiome data will be integrated with detailed information about nutrition, as well as anthropometric, metabolic, and genetic data, to better understand the genetic and environmental factors that contribute to human adaptation to diet. For example, gut bacteria in pastoralists who drink large quantities of milk may be enriched for species that can metabolize the sugar lactose present in milk and, thus, may be informative for studying factors contributing to lactose tolerance, as well as for understanding gene, culture, and bacterial co-adaptation at a larger scale. The project will make a number of significant contributions to the fields of anthropology, genetics, microbiology, and evolutionary biology. Given the existing gap in our knowledge of African genetic and phenotypic diversity relative to other geographic regions, the publically-available data generated by the research will be an important resource for anthropologists, microbiologists, and genetic researchers, contributing to studies of human origins and the design and interpretation of disease association studies. Additionally, because the gut microbiome has a large influence on nutrition, metabolism and immune response, this research project could have an important impact on understanding risk factors for diabetes, infectious disease and under-nutrition. And through the collaborative research, this project also will contribute significantly to the research training of both American and African students and scientists.