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Effect of bacterial monoassociations (Akkermansia muciniphila) on development of type 1 diabetes and immune parameters in ex-germ-free NOD mice
Němec, Dušan ; Funda, David (advisor) ; Zadražil, Zdeněk (referee)
Type 1 diabetes (T1DM) is an autoimmune condition affecting around 0,4 % of general population and its prevalence is still increasing. T1DM is a multifactorial disease, and it develops under the forces of various environmental and hereditary factors. Gut microbiota is recently one of the most relevant environmental features of autoimmunity, including T1DM. Healthy gut microbiota is characterized especially by its variability. However, there has been an effort to determine critical bacteria that can either drive or suppress T1DM development. Akkermansia muciniphila is among those potentially protective bacteria. This diploma thesis examined changes of immune parameters, such regulatory T cells, NK cells, γδ T cells and expression of IFNγ, IL-10 and IL-17, and their correlation with T1DM onset in A. muciniphila- monoassociated ex-germ-free NOD mice compared to germ-free (GF) and specific-pathogen- free (SPF) controls. Furthermore, the second part of the thesis, NOD-SCID adoptive transfer provided an insight into whether diabetogenic ability of NOD mice-derived splenocytes differ in A. muciniphila vs GF and SPF controls. Minor differences were found in immune parameters among various cell populations, with the most prominent increased IL-10 expression in A. muciniphila-monoassociated mice compared to...
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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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