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Microbial transplantation and its effect on the course of ulcerative colitis
Březina, Jan ; Drastich, Pavel (advisor) ; Šťovíček, Jan (referee) ; Janoštiak, Radoslav (referee)
The complex etiopathogenesis of idiopathic inflammatory bowel diseases (IBD) remains unclear, with one of the main suspected causes being the dysregulation of mucosal immunity in response to specific components of the gut microbiome. This dissertation investigates the potential of faecal microbiota transplantation (FMT) as an innovative therapeutic intervention aimed at modifying the microbiome and influencing the course of IBD. FMT, involving the transfer of stool from a healthy donor to the patient, has proven highly effective in the treatment of recurrent Clostridioides difficile colitis, where it is already considered a standard therapeutic procedure. However, in relation to IBD, FMT remains an experimental method, predominantly used in clinical studies. Current systematic reviews indicate that the effect of FMT on ulcerative colitis (UC) is variable, both in terms of achieving remission and clinical response. Recent randomized controlled trials for UC, in accordance with our presented data, show a mild to moderate effect of FMT in this indication. The effectiveness of FMT is influenced by a range of factors, particularly the correct selection of donor or donors, the diversity of their microbiome, methods of application, and frequency of administration. In the case of Crohn's disease, the data...
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Fungal Microbiota and Inflammatory Bowel Disease
Vančíková, Sabína ; Kostovčíková, Klára (advisor) ; Dobeš, Jan (referee)
Inflammatory bowel disease (IBD) is a term for the gastrointestinal tract's chronic inflammatory disorders, evincing growing worldwide prevalence. Commonly, IBD is divided into two major subgroups, Crohn's disease (CD) and ulcerative colitis (UC). Despite intensive efforts, IBD etiology and development mechanisms are not fully understood. Gut barrier dysfunction, dysbiosis, and overreactive immune response to gut microbiota appear to have a significant impact. While bacteria are the most studied gut inhabitants, research on the role of fungal microbiota (mycobiota) in IBD lags behind. This diploma thesis aimed to study immune responses to gut mycobiota in IBD. Levels of antifungal antibodies against gut residents and biomarkers relevant to gut barrier damage and microbial translocation were measured in the sera of IBD patients and healthy individuals. Sera of individuals diagnosed with UC, CD, and IBD associated with primary sclerosing cholangitis (PSC-IBD) were used. Since continuous intestinal macrophage activation is a feature of IBD, the effect of selected fungal mycobiota species on the reactivity of peripheral blood-derived macrophages from healthy donors was assessed in vitro. The levels of serum antibodies against mycobiota components were higher in IBD patients than in controls, and the...
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Pathophysiology of inflammatory bowel disease. Relation to primary scklerosing cholangitis, liver transplantation and carcinogenesis.
Bajer, Lukáš ; Drastich, Pavel (advisor) ; Živný, Jan (referee) ; Procházka, Vlastimil (referee)
Inflammatory bowel disease (IBD) represents a group of multifactorial illnesses with increasing incidence worldwide. Crohn's disease (CD) and ulcerative colitis (UC) are the two most thoroughly defined phenotypes of IBD. IBD associated with primary sclerosing cholangitis (PSC) - a progressive biliary disease leading to cirrhosis and liver failure - is considered as specific IBD phenotype (also referred to as 'PSC - IBD') due to its clinical and pathophysiological characteristics. The aim of the experimental part of this thesis was to define specific features of PSC - IBD in the key areas of IBD pathogenesis. These are: microbiota composition, gut - barrier failure, genetic predisposition and aberrant cellular and antibody immune response. Furthermore, the other goals were to describe relation of IBD status and activity to liver transplantation (LTx) and carcinogenesis based on thorough analysis of clinical data in patients under surveillance at the liver transplantation unit. Using the next-generation parallel sequencing technology, we discovered specific bacterial and mycobial features of gut microbiota composition in PSC - IBD which significantly differed from UC and healthy controls recruited from Czech general population. Moreover, we identified numerous seral biomarkers distinguishing CD, UC...
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