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Sökning: swepub > Umeå universitet > Hernell Olle > Övrigt vetenskapligt/konstnärligt

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  • Nordyke, Katrina, et al. (författare)
  • Epidemiological research drives a paradigm shift in complementary feeding : the celiac disease story and lessons learnt
  • 2010
  • Ingår i: Drivers of Innovation in Pediatric Nutrition. - : S. Karger. - 9783805594547 - 9783805594554 ; , s. 65-79
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Breast milk is the initial natural food for infants, but already during the second half year complementary feeding is essential. Epidemiological research, first on celiac disease and later on atopic diseases, has driven a paradigm shift with respect to most favorable age to introduce complementary feeding. Simplified, this implies a shift from later to earlier introduction, which is now taken into account in recommendations on infant feeding. Complementary feeding, including all foods, should not be initiated for any infant before 4 months of age, and not later than around 6 months, including infants with elevated disease risk (e.g. for celiac disease or atopic diseases). Motivating reasons could be that ongoing breastfeeding provides an 'immunological umbrella' and/ or a different age interval gives a 'window of opportunity' for developing oral tolerance towards gluten and other food antigens. This will for some infants be in conflict with recent WHO recommendations on exclusive breastfeeding for 6 months. Epidemiology has evolved over time and could, if increasingly used, contribute even more to innovations in pediatric nutrition and other phenomena related to population health.
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  • Sjöberg, Veronika, 1980- (författare)
  • Immune response of the small intestinal mucosa in children with celiac disease : impact of two environmental factors, resident microbiota and oats
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Celiac disease (CD) is an immune-mediated enteropathy caused by permanent intolerance to dietary gliadin in wheat gluten and related prolamines in barley and rye. The pathogenesis of CD is still unknown and several different environmental factors have been associated with CD, such as dysbiosis of the microflora. In this translational study we investigated the immune status and the interplay of T-cells and Tregs in the mucosa of children with CD and controls, as well as the immune status in treated CD patients, provoked by either dietary oats, CD associated bacteria or gluten.The major findings in the studies were: First, indicators of extrathymic T-cells maturation (ETCM), i.e., the RAG1 enzyme required for recombination of the T cell receptor (TCR) genes and the preTα-surrogate chain in the immature TCR, were both expressed at lower levels in CD patients compared to controls. In addition, IELs expressing RAG1 were less abundant in CD patients compared to controls. The levels of these two indicators stayed low in treated CD patients as well, suggesting that impaired capacity of ETCM is an inherent feature of CD patients. Second, IL-17A, a cytokine involved in both inflammation and anti-bacterial responses was increased in active CD. The major cellular source was CD8+IELs. Furthermore, ex vivo challenge of biopsies from treated CD patients with gluten and with CD-associated bacteria induced an IL-17A response. The CD-associated bacteria also influenced the magnitude of the IL-17A response to gluten. Third, we investigated the effect of dietary oats on local immune status in the intestinal mucosa by comparing CD patients receiving GFD with and without oats. 22 different mRNAs for immunity effector molecules and tight junction proteins were analyzed. We found that expression of two down-regulatory cytokines, two activating NK-receptors and the tight-junction protein claudin-4 normalized in patients on a standard GFD while they did not normalize in patients on a GFD with oats. Fourth, we analyzed the expression level of mRNAs for chemokines, cytotoxic effector molecules, NK-receptors and their ligands in IELs and epithelial cells. Expression levels of several of these genes follow disease activity, suggesting massive recruitment of immune cells by both cell types accompanied by increased IEL-mediated cytotoxicity in the epithelium of inflamed mucosa.In this thesis we have identified three potential risk factors for development of CD: 1) an inherent lower level of ETCM in the small intestinal mucosa than in controls. This could lead to decreased generation of regulatory T cells and less capacity to tolerate gluten and adapt to the local milieu in the mucosa. 2) Dysbiosis of the resident microbiota with increased IL-17A production that could promote local inflammation and immune cell infiltration as well as antibacterial reactions. 3) Dietary oats may provoke a local immune response in a sub-population of CD patients. These patients should probably avoid oats in their GFD but larger studies are needed.
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