The effects of diet and the microbiota in determining host health

项目总结 在过去的50年里，炎症性疾病的发病率一直在增加，而环境原因，如 饮食，都有牵连。通过西方化，世界变得越来越相似，而西方的饮食(即富含 我们吃的动物脂肪和蛋白质)可能会影响正常的宿主生理。我们肠道内的微生物(即我们的 微生物区系)受饮食的影响很大，导致每个物种的丰度发生变化，而我们饮食中的食物 同样被存在于我们肠道中的细菌的特定新陈代谢能力所改变。内部的变化 细菌种类和代谢产物可以反过来影响宿主的生理和解剖结构的变化。具体地说，两者 饮食成分和微生物区系已被证明影响免疫系统的教育。因此， 我们的饮食、我们的微生物区系和我们的生理系统代表着一个独特的复杂系统，它影响着我们的健康。为了获得一份 更好地了解这些相互作用以及它们可能如何与炎症性疾病发病率的增加有关， 这项建议将量化饮食和微生物区系如何影响WT特定病原体无(SPF)小鼠的健康和 急性葡聚糖硫酸钠(DSS)结肠炎模型和慢性过敏性结肠炎模型的疾病发病机制 T细胞转移性结肠炎模型。目标1-基于我们的初步发现，我们选择了四种对健康有影响的饮食 对急性结肠炎发病机制及严重程度的影响。我们的目标是了解饮食和微生物区系的作用 通过测量宿主细菌丰度的变化，对“健康”小鼠的炎症发展产生影响 细胞因子、免疫细胞、免疫球蛋白、组织学和肠道通透性。喂食这些食物的健康小鼠将允许 美国确定饮食和微生物区系在健康背景下的作用，并确定饮食是否会导致炎症， 即使是低度或亚临床的。此外，AIM 1将提供有价值的数据，这些数据可以解释为什么我们的一些 在目标2中，饮食导致结肠炎的严重程度比其他饮食更严重，在那里我们将检查复杂饮食的协同作用 (即纤维和蛋白质的混合物)和微生物区系对急性和慢性结肠炎的严重性都有影响。 此外，我们将开发一个体内数据驱动的蛋白质和可发酵纤维之间的统计模型， 潜在地为炎症性肠病患者开发新的饮食疗法 疾病。通过系统地扰乱这些模型中的宿主饮食并测量发生在 微生物区系和寄主生理学，我们可以更好地了解饮食在维持和控制 疾病。

PROJECT SUMMARY The incidence of inflammatory diseases has been increasing over the past fifty years, and environmental causes, such as diet, are implicated. The world is becoming more similar through westernization, and the western diet (i.e. diets rich in animal fat and protein) that we eat could be influencing normal host physiology. The microbes within our gut (i.e. our microbiota) are greatly influenced by diet, leading to changes of abundance of each species, while the food within our diet is likewise altered by specific metabolic capabilities of the bacteria that are present within our guts. The changes within bacterial species and metabolites can in turn effect changes within physiology and anatomy of the host. Specifically, both dietary components and the microbiota have been demonstrated to influence the education of the immune system. Thus our diets, our microbiota, and our physiology represent a uniquely complex system that influences our health. To gain a better understanding of these interactions and how they might relate to the increased incidence of inflammatory diseases, this proposal will quantify how diet and the microbiota influence health in WT specific pathogen free (SPF) mice and disease pathogenesis in two colitis models, the acute dextran sodium sulfate (DSS) colitis model and the chronic adoptive T cell transfer colitis model. Aim 1 – Based on our preliminary findings, we have selected four diets that exert an influence on the pathogenesis and severity of acute colitis. We aim to understand the role that diet and the microbiota has upon the development of inflammation in “healthy” mice by measuring changes in bacterial abundance, host cytokines, immune cells, immunoglobulins, histology, and intestinal permeability. Healthy mice fed these diets will allow us to determine the role of diet and the microbiota in the context of health and establish if diet can cause inflammation, even if it is low-grade or subclinical. In addition, Aim 1 will provide valuable data that could explain why some of our diets cause greater colitis severity than others in Aim 2, where we will examine the synergistic roles that complex diets (i.e. mixtures of fibers and protein) and microbiota have upon both acute and chronic colitis severity. Furthermore, we will develop an in vivo data-driven statistical model between protein and fermentable fibers, potentially leading to the development of novel dietary treatments for patients suffering from inflammatory bowel disease. By systematically perturbing the host diet in these models and measuring the changes that occur within the microbiota and host physiology, we can gain a better understanding of the role of diet in the maintenance and control of disease.