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Host-microbe interactions and its consequences for intestinal inflammation and carcinogenesis
Kejzlarová, Leona ; Kverka, Miloslav (advisor) ; Smrž, Daniel (referee)
A number of physiological and pathological processes, including the transition from chronic inflammation to cancer, are affected by commensal microbes. However, abundance of microbes and ability to produce active metabolites in the intestine depend on environmental factors, particularly diet. Microbes can influence this process in two ways, by producing genotoxic substances that directly damage the epithelium or by stimulating the inflammatory response. The aim of my thesis was to study the interaction among gut microbiota, diet and the immune system with the subsequent influence on the development of colorectal cancer (CRC) in an experimental mouse model. Animals were fed synthetic diets containing either normal amounts of animal protein (17%; KD) or elevated amounts of animal protein (51%; HPD) throughout the experiments. Two weeks after the diets were introduced, intestinal tumors were induced by administering azoxymethane (AOM) and inducing acute inflammation with 2% sodium dextran sulfate one week after AOM injection. At the end of the experiment I evaluated the number of tumors in the colon and the status of the immune response in the intestine, mesenteric lymph nodes and spleen. To study the effect of macrophages, a similar experiment was performed in animals with depleted macrophages using...
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Roles of environmental factors and microbiome in type 1 diabetes
Novotná, Kateřina ; Funda, David (advisor) ; Cahová, Monika (referee)
Type 1 diabetes mellitus (T1DM) is an insulin-dependent autoimmune disease. Its onset is characterized by an autoreactive self-destruction of β-cells within pancreatic islets. T1DM is influenced by multiple genetic predispositions, but since the incidence of the disease has increased dramatically in the past decades, especially in developed, western-type countries, the importance of the environmental factors has become obvious. There are various significant environmental influences that need to be addressed in the equation of variables. This bachelor thesis deals with the environmental variables and their mechanisms in T1DM and focuses on several areas of interest. It introduces frequently used spontaneous animal model of T1DM, pathogenetic mechanisms and T-cells in T1DM as well as regulatory immune cells and their mechanisms, in the light of hygiene and another hypothesis. Next it addresses the role of intestinal microbiota, dietary factors, mucosal immunity, their mechanisms and interactions in T1DM and extends to other, less researched, but important environmental variables such as circadian rhythm in connection with circadian gene expression depending on the rhythmicity of light/dark rotation and timing of food intake throughout the day, psychological/oxidative stress, and the effects of...
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Dietary factors in the development of type 1 diabetes
Fiala, Marek ; Funda, David (advisor) ; Grobárová, Valéria (referee)
Type 1 diabetes mellitus is an autoimmune disease which develops in genetically susceptible individuals and whose incidence rapidly increases, especially in developed countries. Type 1 diabetes is believed to be strongly associated with the environment: viruses, stressful life events or the absence of exposition to antigens in early life increase its incidence. Antigens to which we are expressed continuously are food antigens. Gluten, milk proteins or the intake of vitamin D precursors clearly influence type 1 diabetes pathogenic process. This bachelor's thesis aims to describe our current knowledge on the role of dietary factors in type 1 diabetes, their possible immune mechanisms and also interplay with other environmental factors. Key words: type 1 diabetes, dietary factors, gluten-free diet, immune mechanisms, prevention, NOD mouse, mucosal immunity
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Slizniční imunita, střevní mikroflora a nespecifické střevní záněty
Tlaskalová, Helena ; Štěpánková, Renata ; Sokol, Dan ; Rossmann, Pavel ; Cukrowska, Božena ; Hudcovic, Tomáš ; Tučková, Ludmila ; Kozáková, Hana ; Řeháková, Zuzana ; Hrnčíř, Tomáš ; Drastich, Pavel ; Frolová, Lenka ; Powrie, F. ; Uhlig, H. ; Bland, P. W.
Etiological role of intestinal microflora and abberant function of mucosal immunity in development of inflammatory bowel disease is discussed. Animal models of human IBD are described and characterized
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