The relationship between host diet, the gut microbiota, and host transcription

描述（由申请人提供）：我们肠道中的一组微生物（即，我们的微生物群）以及我们摄入的食物，都代表着环境对我们生理的干扰。当我们食用不同的食物时，我们肠道中每种物种的丰度都会发生显着变化，而这些食物的化学成分也会在我们的肠道中通过居住在那里的微生物的特定代谢能力进行独特的修改。因此，我们的饮食，我们的微生物群和我们的生理学代表了一个独特而复杂的相互作用的基因，有机体和营养素系统。计算建模提供了一系列工具来理解和控制复杂的系统;正是在这种情况下，我们的实验室继续开发统计模型，以了解我们的饮食，微生物群和健康之间的关系。为了实现这些长期目标，本申请有两个具体目标，重点是涉及从不同个体分离的六种定义的人源性微生物的预测模型。目标1 -基于我们之前成功使用携带10种人类肠道细菌的特定群落的gnotobiotic小鼠来预测每个物种对宿主饮食特定成分扰动的丰度，我们的目标是通过模拟六种定义的微生物群的反应来了解我们的饮食和我们的肠道微生物之间的定量关系，这些微生物群从不同的人类供体中分离并移植到gnotobiotic小鼠中，对八种常见人类食物的饮食扰动。这些模型将提供对控制饮食和微生物群之间规则的人际变化的洞察（例如，从两个不同供体分离的大肠杆菌对相同食物的反应方式相似）。此外，目标1将提供有关饮食和微生物群之间关系的有价值的初步数据，这些数据将用于优化目标2的设计，我们将在目标2中定义饮食，肠道微生物群和宿主转录变异之间的相互关系。通过在无菌动物和携带目标1中定义的微生物群的动物的背景下系统地干扰宿主饮食，我们计划对宿主小肠、结肠和肝脏中受特定饮食成分、微生物群或饮食和微生物群组合影响的转录变化进行建模和量化。

DESCRIPTION (provided by applicant): The set of microbes in our gut (i.e., our microbiota) as well as the food we ingest, both represent environmental perturbations to our physiology. The abundance of each species in our gut is dramatically altered as we consume different foods, while the chemical composition of these of foods is likewise uniquely modified in our intestines by the specific metabolic capabilities of the group of microbial organisms that resides there. Thus our diets, our microbiota, and our physiology represent a unique and complex system of interacting genes, organisms, and nutrients. Computational modeling provides a series of tools to understand and control complex systems; it is in this vein that our lab continues to develop statistical models to understand the relationship between our diet, our microbiota, and our health. Towards these long-term goals, this application has two specific aims focused on predictive models involving six defined human-derived microbiotas isolated from different individuals. Aim 1 - Building on our previous success in using gnotobiotic mice harboring a defined community of 10 human-gut bacteria to predict the abundance of each species in response to specific ingredient perturbations to the host diet, we aim to understand the quantitative relationship between our diets and our gut microbes by modeling the responses of six defined microbiota, isolated from different human donors and transplanted into gnotobiotic mice, to diet perturbations of eight commonly eaten human foods. These models will provide insight into the interpersonal variations governing the rules between diet and the microbiota (e.g., does an Escherichia coli species isolated from two different donors response to similar ways to the same food). In addition, Aim 1 will provide valuable preliminary data about the relationship between diet and the microbiota that will be used to optimize the design of Aim 2 where we will define the interrelationship between diet, the gut microbiota, and host transcriptional variation. By systematically perturbing the host diet in the context of germ-free animals and animals harboring the defined microbiotas from Aim 1, we plan to model and quantify the transcriptional changes in the host small intestine, colon, and liver that are influenced by specific diet ingredients, the microbiota, or a combination of diet and the microbiota.