The effects of diet and the microbiota in determining host health

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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.