DISSERTATION RESEARCH: Quantifying Nitrogen Limitation in the Gut Microbiota

不同种类的营养物质的可用性可以决定哪些物种能够共同生活。当微生物（如细菌）生活在动物（如人类）体内时，它们可能会竞争有限的营养物质（如氮），也可能会相互合作以获得相同的营养物质。这个项目将研究人类和肠道中的细菌如何控制对氮的需求。人类从饮食中获取氮，肠道细菌从宿主体内获取氮。这种细菌可以与人类在吞咽食物中争夺氮，也可以通过人类排泄到肠道中的物质来“喂养”它们。研究人员将重点关注肠道中氮的竞争，并测试它对确定哪种细菌可以在那里生存是否重要。这项工作的结果可能有助于设计需要改变病人和家畜肠道内细菌群落的治疗方法。氮在肠道中受到限制的假设来自于这样一种观察，即到达大肠的大多数不可消化的物质都是缺乏氮的，因此，大多数肠道微生物群几乎没有可利用的氮。这导致了两个可验证的预测。首先，环境（非微生物）碳氮比（C:N）存在纵向梯度，健康肠道中饮食来源的氮耗竭。其次，细菌使用的大部分氮必须来自宿主分泌物。这些预测将通过测量肠道碳氮比和使用稳定同位素示踪剂研究来确定膳食氮的去向和细菌氮的来源来验证。最后，为了确定氮有效性的变化是否会改变肠道微生物群落组成，我们将在不同氮有效性水平下进行体外共培养竞争实验。

The availability of different types of nutrients can determine which species are able live together. When microbes (such as bacteria) live inside animals (such as humans), they may compete for a limited nutrient (such as nitrogen) or may cooperate with each other to acquire that same nutrient. This project will examine how humans and the bacteria in their guts manage their needs for nitrogen. Humans get nitrogen from their diet, and gut bacteria get nitrogen from inside their human hosts. The bacteria can either compete with humans for nitrogen in swallowed food or they can be "fed" through material that humans excrete into the gut. The researchers will focus on competition for nitrogen in the gut and test whether it is important in determining which species of bacteria can live there. The results of this work may help in the design of treatments that require a change in the community of bacteria living in the guts of sick people and domestic animals.The hypothesis that nitrogen is limiting in the gut comes from the observation that most indigestible material reaching the large intestine is nitrogen poor and, therefore, there is little nitrogen available to most of the gut's microbiota. This leads to two testable predictions. First, there is a longitudinal gradient in the environmental (non-microbial) carbon-to-nitrogen (C:N) ratio and a depletion of diet-sourced nitrogen along a healthy gut. Second, much of the nitrogen used by bacteria must come from host secretions. These predictions will be tested by measuring C:N ratios along the gut and by using stable isotope tracer studies to identify the fate of dietary nitrogen and the source of bacterial nitrogen. Finally, to determine if changes in nitrogen availability can alter microbial community composition in the gut, in vitro co-culture competition experiments will be conducted under varying levels of nitrogen availability.