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Gut barrier in the pathogenesis and diagnostics of necrotizing enterocolitis and inflammatory bowel disease
Coufal, Štěpán ; Kverka, Miloslav (advisor) ; Nevoral, Jiří (referee) ; Stříž, Ilja (referee)
Disruption of gut microbiota, altered mucosal defense, inappropriate immune response and gut barrier damage are all typical features in the pathogenesis of both necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). Despite of intensive research, the exact pathogenesis of both diseases remains unclear and the diagnostics and outcome prediction are still problematic. Therefore, we analyzed the role of gut-associated and inflammatory biomarkers, with respect to different aspects of gut barrier dysfunction in the pathogenesis of both disease, with the aim to improve the diagnostics and to predict the disease course and outcome. Using ELISA, we found that patients who will later develop NEC have significantly higher intestinal fatty acid-binding protein (I-FABP) than infants who will later develop sepsis already in first hours after NEC suspicion. Urinary I-FABP had high sensitivity (81%) and specificity (100%) and its addition to currently used gold standard for NEC diagnosis increased its sensitivity and negative predictive value. We found that serum amyloid A (SAA) was the strongest factor for prediction of the most severe stage of NEC. The combination of intestinal and liver FABP with SAA predicted the length of hospitalization in NEC patients and the low level of SAA predicted short...
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Gut barrier in the pathogenesis and diagnostics of necrotizing enterocolitis and inflammatory bowel disease
Coufal, Štěpán
Disruption of gut microbiota, altered mucosal defense, inappropriate immune response and gut barrier damage are all typical features in the pathogenesis of both necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). Despite of intensive research, the exact pathogenesis of both diseases remains unclear and the diagnostics and outcome prediction are still problematic. Therefore, we analyzed the role of gut-associated and inflammatory biomarkers, with respect to different aspects of gut barrier dysfunction in the pathogenesis of both disease, with the aim to improve the diagnostics and to predict the disease course and outcome. Using ELISA, we found that patients who will later develop NEC have significantly higher intestinal fatty acid-binding protein (I-FABP) than infants who will later develop sepsis already in first hours after NEC suspicion. Urinary I-FABP had high sensitivity (81%) and specificity (100%) and its addition to currently used gold standard for NEC diagnosis increased its sensitivity and negative predictive value. We found that serum amyloid A (SAA) was the strongest factor for prediction of the most severe stage of NEC. The combination of intestinal and liver FABP with SAA predicted the length of hospitalization in NEC patients and the low level of SAA predicted short...
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Gut barrier in the pathogenesis and diagnostics of necrotizing enterocolitis and inflammatory bowel disease
Coufal, Štěpán ; Kverka, Miloslav (advisor) ; Nevoral, Jiří (referee) ; Stříž, Ilja (referee)
Disruption of gut microbiota, altered mucosal defense, inappropriate immune response and gut barrier damage are all typical features in the pathogenesis of both necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). Despite of intensive research, the exact pathogenesis of both diseases remains unclear and the diagnostics and outcome prediction are still problematic. Therefore, we analyzed the role of gut-associated and inflammatory biomarkers, with respect to different aspects of gut barrier dysfunction in the pathogenesis of both disease, with the aim to improve the diagnostics and to predict the disease course and outcome. Using ELISA, we found that patients who will later develop NEC have significantly higher intestinal fatty acid-binding protein (I-FABP) than infants who will later develop sepsis already in first hours after NEC suspicion. Urinary I-FABP had high sensitivity (81%) and specificity (100%) and its addition to currently used gold standard for NEC diagnosis increased its sensitivity and negative predictive value. We found that serum amyloid A (SAA) was the strongest factor for prediction of the most severe stage of NEC. The combination of intestinal and liver FABP with SAA predicted the length of hospitalization in NEC patients and the low level of SAA predicted short...
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Gut barrier in the pathogenesis and diagnostics of necrotizing enterocolitis and inflammatory bowel disease
Coufal, Štěpán
Disruption of gut microbiota, altered mucosal defense, inappropriate immune response and gut barrier damage are all typical features in the pathogenesis of both necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). Despite of intensive research, the exact pathogenesis of both diseases remains unclear and the diagnostics and outcome prediction are still problematic. Therefore, we analyzed the role of gut-associated and inflammatory biomarkers, with respect to different aspects of gut barrier dysfunction in the pathogenesis of both disease, with the aim to improve the diagnostics and to predict the disease course and outcome. Using ELISA, we found that patients who will later develop NEC have significantly higher intestinal fatty acid-binding protein (I-FABP) than infants who will later develop sepsis already in first hours after NEC suspicion. Urinary I-FABP had high sensitivity (81%) and specificity (100%) and its addition to currently used gold standard for NEC diagnosis increased its sensitivity and negative predictive value. We found that serum amyloid A (SAA) was the strongest factor for prediction of the most severe stage of NEC. The combination of intestinal and liver FABP with SAA predicted the length of hospitalization in NEC patients and the low level of SAA predicted short...
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Role of microbiota in mouse experimental model of psoriasis
Jirásková Zákostelská, Zuzana ; Stehlíková, Zuzana ; Klimešová, Klára ; Rossmann, Pavel ; Dvořák, Jiří ; Novosádová, Iva ; Kostovčík, Martin ; Coufal, Štěpán ; Šrůtková, Dagmar ; Hudcovic, Tomáš ; Štěpánková, Renata ; Rob, F. ; Jůzlová, P. ; Herzogová, J. ; Tlaskalová-Hogenová, Helena ; Kverka, Miloslav
Anotace v anglickém jazyce\n\nMouse model of human psoriasis and gnotobiotic are important tools in understanding the role of gut and skin microbiota in pathogenesis of psoriasis. In our experiments we showed that gnotobiotic mice, as well as conventional mice treated with antibiotics, have milder skin inflammation in comparison with control conventional mice. Treatment with broad spectrum antibiotics led to dramatic shift in gut microbial composition, in particular, we observed extensive increase of order Lactobacillales. To analyze the potential effect of Lactobacillales on skin inflammation, we further monocolonized mice with L. plantarum WCFS1. Also monocolonized mice showed lower skin inflammation in comparison with conventional mice. To understand whether microbial dysbiosis is cause or effect of psoriasis needs to be further investigated.\n\n
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Gut barrier function in pathogenesis of necrotizing enterocolitis
Coufal, Štěpán ; Kverka, Miloslav (advisor) ; Vančíková, Zuzana (referee)
Abstract Necrotizing enterocolitis (NEC) is severe and life-threatening disease of infant gastrointestinal tract (GIT). It is a defect of GIT adaptation to extrauterine life, which affects mostly premature infants and infants afflicted by congenital developmental defects of GIT or heart. Gut barrier disruption and presence of abnormal gut microbiota has eminent role in NEC pathogenesis. Nowadays, the diagnosis of NEC is based on presence of clinical symptoms - abdominal distension, blood in stool and radiologic finding Pneumatosis intestini. However, the symptoms are in early stage of NEC non- specific and do not allow unambiguous distinguishing of NEC from other GIT disorders or sepsis. Aim of this thesis was to extend the understanding of inflammatory response in neonates with NEC and to find applicable biomarker for early diagnosis of NEC and thereby provide quick intervention. Cytokines have important role in immune response regulation. Although the connection between some cytokines and NEC was described, the inflammatory response during NEC was not yet properly stated. The levels of 40 cytokines related to inflammation was shown in this thesis. Intestinal - Fatty Acid Binding Protein (i- FABP) is a small...
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