The effects of diet and the microbiota in determining host health

项目摘要 炎症性疾病的发病率在过去的五十年中一直在增加，并且环境原因，如 饮食，有牵连。世界正通过西方化变得越来越相似，西方饮食（即富含 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）受饮食影响很大，导致每个物种的丰度变化，而我们饮食中的食物 同样会被我们肠道内细菌的特定代谢能力所改变。内的变化 细菌种类和代谢物又可以影响宿主的生理学和解剖学的变化。具体来说，两者 饮食成分和微生物群已被证明影响免疫系统的教育。因此 我们的饮食，我们的微生物群和我们的生理学代表了一个影响我们健康的独特复杂系统。获得 更好地理解这些相互作用以及它们如何与炎症性疾病的发病率增加有关， 该提案将量化饮食和微生物群如何影响无WT特异性病原体（SPF）小鼠的健康， 在两种结肠炎模型（急性葡聚糖硫酸钠（DSS）结肠炎模型和慢性过继性结肠炎模型）中的疾病发病机制 T细胞转移结肠炎模型。目的1 -根据我们的初步研究结果，我们选择了四种饮食， 影响急性结肠炎的发病机制和严重程度。我们的目标是了解饮食和微生物群 通过测量细菌丰度的变化， 细胞因子、免疫细胞、免疫球蛋白、组织学和肠通透性。健康的老鼠喂养这些饮食将允许 我们确定饮食和微生物群在健康环境中的作用，并确定饮食是否会引起炎症， 即使它是低级别或亚临床的。此外，目标1将提供有价值的数据，可以解释为什么我们的一些 饮食导致更大的结肠炎的严重程度比其他目标2，在那里我们将研究协同作用，复杂的饮食 (i.e.纤维和蛋白质的混合物）和微生物群对急性和慢性结肠炎的严重性都有影响。 此外，我们将开发蛋白质和可发酵纤维之间的体内数据驱动统计模型， 这可能导致开发用于患有炎症性肠病的患者的新型饮食疗法， 疾病通过系统地干扰这些模型中的宿主饮食，并测量在宿主体内发生的变化， 微生物和宿主生理学，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.