The protein nutrition of the symbiotic system between /Drosophila/and its gut mic

描述（由申请人提供）：肠道微生物群有助于人类和其他动物的蛋白质营养。这项研究将使用模式昆虫果蝇来确定宿主如何在生理和遗传上与肠道微生物相互作用，以最大限度地提高蛋白质营养以及整体健康和健身。这一建议的基础是，动物的营养生理学和共生是相互依存的，因此只有将动物蛋白质营养视为共生系统时才能充分理解。此外，这种共生系统是高度动态的：微生物群或饮食的扰动可以对蛋白质营养产生重大影响，通过宿主营养生理学与微生物群的组成/功能之间的相互作用起作用，对宿主的健康产生深远影响。果蝇特别适合这项研究，因为它在营养需求方面与人类高度同源，但具有实验优势，即拥有简单的肠道微生物群，可以容易地操纵。果蝇也可以用各种实验性饮食饲养，从而可以测试饮食成分的影响，模仿人类的饮食行为改变。这项拟议的研究将衡量饮食和共生操纵对果蝇蛋白质营养和整体健康和健身的生理后果。它将测试的假设，即宿主的遗传变异的同化和分配的蛋白质前体的基础上的变化，依赖于共生协会最大的健康，并将使用基因组资源和系统分析，以定义的表达网络，支持共生与不同的影响主机蛋白质营养。这项研究将首次了解肠道共生对宿主蛋白质营养的重要性的自然变化机制，与了解人类饮食和营养状况及其对健康的影响直接相关。 公共卫生相关性：肠道中的共生细菌在蛋白质营养中起着重要作用，因此对人类和其他动物宿主的整体健康和健身起着重要作用。拟议的研究将调查肠道微生物影响宿主蛋白质代谢的生理机制，将量化与肠道微生物相互作用的宿主遗传变异，并将构建一个合成基因表达网络来描述共生系统。这项工作将有助于了解支持临床代谢和营养状况的饮食和遗传因素，以及肠道共生对健康的影响。

DESCRIPTION (provided by applicant): The gut microbiota contributes to the protein nutrition of humans and other animals. This study will use the model insect Drosophila melanogaster to determine how hosts interact physiologically and genetically with their gut microbes to maximize protein nutrition as well as overall health and fitness. The basis of this proposal is that the nutritional physiology and symbiosis of animals are interdependent, such that animal protein nutrition can only be understood fully when considered as a symbiotic system. Furthermore, this symbiotic system is highly dynamic: perturbation to the microbiota or diet can have major impact on the protein nutrition, acting through interactions between host nutritional physiology and the composition/function of the microbiota, with profound impacts on the health of the host. Drosophila is particularly amenable to this study because it is highly homologous to humans in its nutritional requirements, but has the experimental advantage of possessing a simple gut microbiota that can be manipulated easily. Drosophila can also be reared on a variety of experimental diets, allowing tests for the effect of diet composition, mimicking dietary behavioral modification in humans. The proposed study will measure the physiological consequences of dietary and symbiotic manipulation on Drosophila on protein nutrition and overall health and fitness. It will test the hypothesis that host genetic variation in the assimilation and allocation of protein precursors underlies variation in dependence on symbiotic associations for maximal health, and will use genomic resources and systems analyses to define the expression networks that underpin symbioses with different impacts on host protein nutrition. This research will achieve the first understanding of the mechanisms underlying natural variation in the significance of the gut symbiosis to host protein nutrition, with direct relevance to understanding human dietary and nutritional conditions and their impacts on health. PUBLIC HEALTH RELEVANCE: Symbiotic bacteria in the gut play an important role in protein nutrition, and therefore to the overall health and fitness of humans and other animal hosts. The proposed study will investigate the physiological mechanisms by which gut microbes impact host protein metabolism, will quantify host genetic variation for interactions with gut microbes, and will construct a synthetic gene expression network to describe the symbiotic system. The work will contribute to understanding the dietary and genetic factors underpinning clinical metabolic and nutritional conditions, and the impacts of gut symbiosis on health.