The main aim of this thesis is to analyse restaurants in Prague which offer special dishes for people who suffer from celiac disease. Theoretical part consists of definition and history of celiac disease, symptoms of celiac disease etc. One of the aims of the practical part is to create a free city map with marked restaurants suitable for people who suffer from celiac disease. The author conducted a survey among tourists whether they would appreciate this kind of map.

The only treatment for celiac disease (CeD), an autoimmune disorder triggered by the ingestion of gluten, is lifelong adherence to a gluten-free diet (GFD). CeD and the GFD have been shown to be associated with low quality of life (QoL). In some individuals, such a strict diet can lead to disordered eating attitudes and behaviors. The purpose of this study was to better understand the extent to which disordered eating attitudes and behaviors may be common in a sample of adults diagnosed with CeD, as well as the relationship with various factors and QoL measures, including anxiety and depression. The study is a cross sectional pilot study of 50 individuals with CeD. Patients between the ages of 18 to 45 years old (mean=29.56, SD=7.40) with a biopsy-proven CeD diagnosis, following a GFD for at least a year (mean=7.20, SD=5.31) with no previous or current eating disorder diagnosis were recruited. In this study, suggestive ED (based on EDDS) and DE (based on EPSI) were present, but low (2% suggestive diagnosis of BED, 12% suggestive diagnosis of OSFED as per DSM-V). The distribution of the self-reported food attitudes and behaviors measures (CD-FAB scores) were spread out around the mean 36.96 (15.30) with a maximum score of 66 out of a possible 77. The CD-FAB may have utility in identifying adults with CeD that may be at risk for disordered eating attitudes and behaviors, particularly those in the first few years after diagnosis. It likely has limited utility in identifying suggestive EDs (as per EDDS) and DE (as per EPSI). The main factors that were associated with higher CD-FAB scores were BMI, number of symptoms, years since diagnosis, diet adherence and personality characteristics. Seven years after diagnosis seems to be an important cut-point in how participants rated food attitudes, fear responses and adaptive responses on the CDFAB scales. Higher CD-FAB scores had a significant and meaningful association with QoL scores. Participants recruited during the COVID-19 pandemic had significantly lower CD-FAB scores and higher QoL scores compared to those recruited pre-pandemic; despite not having significant differences in any other demographic characteristics.

Tesis por compendio / [EN] Celiac disease (CD) is a chronic enteropathy triggered by cereal gluten proteins in genetically predisposed individuals. The etiology is strongly associated with the genes of the human leukocyte antigen (HLA) encoding the DQ2/DQ8 molecules. Most CD patients carry this genotype but this is also present in the 40% of the general population and only a small percentage develops the disease. Thus, the HLA-DQ genotype is necessary but not solely responsible for the disease development. Gluten is the main environmental trigger but its intake neither fully explains the onset nor its clinical manifestations. Other environmental factors (e.g. early feeding practices, infections, intestinal microbiota) have been associated with the risk of developing CD. The only treatment for CD patients is the adherence to a gluten free diet (GFD), but the compliance with this dietary strategy is complicated because gluten is present in many foods. Therefore, the identification of modifiable environmental factors that contribute to CD onset is critical for the development of strategies to reduce its incidence. Observational studies in CD patients revealed imbalances in the intestinal microbiota which could contribute to the pathogenesis of the disease. It has been proposed that these imbalances are not only a secondary consequence of the disease but could also be a predisposing factor. To understand whether gut microbiota imbalances play a role in CD onset and pathogenesis, in vitro, animal and human prospective and intervention studies have been conducted in the context of the present PhD Thesis. The global aim of this Thesis has been to improve the understanding of the role played by intestinal microbiota in the pathogenesis and risk of CD, and the possibilities of contributing to disease prevention and treatment by modulating gut microbiota composition. Chapter 1 includes two in vitro studies investigating the influence of components of the gut microbiota (bifidobacteria and enterobacteria) on the maturation and functions of immunocompetent cells (dendritic cells), and on gluten toxicity in the intestinal epithelium (Caco-2 cells). We have observed that some Bifidobacterium strains are able to reduce the activation of dendritic cells and ameliorate the toxicity of gluten on intestinal epithelial cells. In Chapter 2 the effects of the administration of Bifidobacterium longum CECT 7347 was evaluated in an in vivo model of gluten induced enteropathy in newborn rats, resulting in a reduced proinflammatory cytokine production in the small intestine and CD4+T cell numbers in peripheral blood. Chapter 3 includes two observational studies in humans to unravel whether breast-feeding and human milk composition and/or the host genotype (HLA-DQ) are related to the microbiota, thereby influencing the later development of CD. We concluded that both factors may contribute to the early intestinal colonization of the infant's gut, influencing the Bifidobacterium spp. numbers. Human milk composition also varies in CD and non-CD mothers, modifying the supply of bifidobacteria and protective immune factors to the offspring. Finally, in Chapter 4 we have studied the potential beneficial effects of the administration of B. longum CECT 7347 in addition to the GFD to children with newly diagnosed CD. This study demonstrates that the bifidobacteria slightly reduces serum inflammatory markers and restored the gut microbiota composition. / [ES] La enfermedad celíaca (EC) es una enteropatía crónica de carácter autoinmune que sufren individuos genéticamente predispuestos tras la ingesta de gluten. La etiología está asociada con los genes del sistema "Antígeno Leucocitario Humano" (HLA) que codifican las moléculas DQ2/DQ8. Los pacientes con EC presentan este genotipo, sin embargo este también está presente en ¿40% de la población general y sólo un pequeño porcentaje desarrolla la enfermedad. Por lo tanto, el genotipo HLA-DQ resulta necesario pero no suficiente para que se desarrolle la enfermedad. El gluten es el principal desencadenante pero su ingesta tampoco explica su desarrollo ni sus manifestaciones clínicas. Otros factores ambientales (p.e. la lactancia, infecciones, microbiota intestinal) se han asociado con el riesgo de desarrollar la EC. El único tratamiento para los pacientes celíacos es el seguimiento de una dieta exenta de gluten (DEG), sin embargo su cumplimiento es complicado debido a que el gluten está presente en la mayoría de los alimentos procesados. Por ello, la identificación de factores ambientales modificables que contribuyan al desarrollo de la enfermedad, resulta fundamental para desarrollar estrategias que permitan reducir su incidencia. Estudios observacionales realizados en pacientes con la EC, han demostrado la existencia de desequilibrios en su microbiota intestinal, que podrían contribuir a la patogénesis de la enfermedad. Se ha propuesto que estos desequilibrios no son sólo una consecuencia secundaria de la EC, sino que podrían ser un factor predisponente. Para entender si la microbiota está implicada en el desarrollo y patogénesis de la EC, en la presente Tesis se han desarrollado estudios in vitro, con animales y estudios prospectivos y de intervención en humanos. El objetivo de esta Tesis ha sido avanzar en el conocimiento de la función que la microbiota intestinal desempeña en la patogénesis de la EC, así como, acerca de las posibilidades de tratar o prevenir esta enfermedad mediante la modulación de la composición de la microbiota intestinal. El Capítulo 1 incluye dos estudios in vitro en los que se ha estudiado la influencia de componentes de la microbiota intestinal (bifidobacterias y enterobacterias) en la maduración y las funciones de células inmunocompetentes (células dendríticas), y en la toxicidad del gluten en el epitelio intestinal (células Caco-2). Hemos observado que algunas cepas de Bifidobacterium son capaces de reducir la activación de las células dendríticas y de reducir la toxicidad del gluten sobre el epitelio intestinal. En Capítulo 2 incluye el estudio de los efectos de la administración de B. longum CECT 7347 en un modelo de enteropatía inducida por gluten en ratas recién nacidas, observándose una reducción de citoquinas proinflamatorias en el intestino y de células T CD4+ en sangre periférica. El Capítulo 3 incluye dos estudios observaciones en humanos en los que se ha investigado si la lactancia y composición de la leche materna y/o el genotipo (HLA-DQ) están relacionados con la microbiota y, si así, podrían influir en el desarrollo de la EC. Concluimos que ambos factores contribuyen a la colonización intestinal del niño en los primeros meses de vida, afectando especialmente al número de Bifidobacterium spp. La composición de la leche maternal varía entre madres celíacas y sanas, lo que podría modificar el aporte de bifidobacterias y factores inmunológicos protectores al lactante. Por último, en el Capítulo 4 incluye el estudio del potencial efecto beneficioso de la administración de B. longum CECT 7347 junto con la DEG en niños recién diagnosticados de EC. Este estudio demuestra que la bifidobacteria ligeramente reduce los marcadores inflamatorios en sangre periférica y contribuye a restablecer la composición de la microbiota intestinal. / [CA] La malaltia celíaca (MC) és una enteropatia crònica provocada per les proteines del gluten de cereals en individus predisposats genèticament. L'etiologia està fortament associat amb els gens de l'antigen leucocitari humà (HLA). Pacients amb MC porten aquest genotip però també està present en aproximadament el 40% de la població general i només un petit percentatge (1-3%) es desenvolupa la malaltia. Per tant, HLA-DQ genotip és necessària, però no l'únic responsable. El gluten és el principal desencadenant ambiental però la seva ingesta no explica completament l'inici ni les seves manifestacions clíniques. Altres factors ambientals, com la microbiota intestinal, s'han associat amb el risc de desenvolupar CD. Els estudis observacionals en pacients amb MC van revelar desequilibris en la microbiota intestinal que podria contribuir a la patogènesi de la malaltia. S'ha proposat que aquests desequilibris no només són una conseqüència secundària de la malaltia, però també podria ser un factor predisponent. Per entendre si els desequilibris microbiota intestinal podrien tenir un paper en l'aparició de CD, un estudi prospectiu amb el nen en risc la família està en marxa. L'únic tractament per als pacients amb EC és l'adherència a una dieta lliure de gluten, però el seu compliment és complicada a causa del gluten està present en molts aliments. La identificació de factors ambientals modificables que contribueixen a l'aparició de CD és fonamental per a les estratègies de desenvolupament que porten a una reducció de la incidència. Aquest pot ser el cas per als components de la microbiota intestinal, l'adquisició podria ser modulada per factors ambientals i dietètics. L'objectiu global de la tesi és desentranyar els coneixements actuals sobre el paper exercit per la microbiota intestinal en la patogènesi de l'EC, i les possibilitats de contribuir a la prevenció i tractament de la malaltia mitjançant la modulació de la composició de la microbiota intestinal En el Capítol 1 hem estudiat l'ús de models in vitro de la influència de la microbiota intestinal durant la maduració i funcions del sistema immunològic (cèl·lules dendrítiques), i les interaccions entre el gluten i intestinal intestí i la resposta de l'epiteli intestinal resultant d'aquesta interacció. Hem observat que alguns ceps de Bifidobacterium són capaços de reduir l'activació del sistema immune i millorar la resposta nociva de l'epiteli intestinal a l'estimulació amb gluten. En el Capítol 2 hem estudiat els efectes de l'administració d'una soca de Bifidobacterium (B. longum CECT 7347) per a un model animal de rates nounades. El tractament amb els bacteris es va associar amb una reducció en la producció de citocines proinflamatòries i la resposta immune de cèl·lules T CD4 +. En el Capítol 3 es va descriure que alguns genètic (HLA-DQ genotip) i factors ambientals (llet materna) influeixen en la colonització intestinal primerenca, especialment en Bifidobacterium spp., que poden influir en l'aparició de CD més tard. Finalment, en el Capítol 4 s'ha estudiat l'efecte probiòtic de l'administració de B. longum CECT 7347 en nens acabats diagnosticats d'EC i el seu paper en el restabliment de la salut intestinal. / Olivares Sevilla, M. (2015). Influence of intestinal microbiota in celiac disease pathogenesis and risk [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/58768 / TESIS / Premios Extraordinarios de tesis doctorales / Compendio

Indiana University-Purdue University Indianapolis (IUPUI) / This research explores the illness experiences of women and men who received a Celiac Disease Diagnosis as an adult in addition to the impact it had on their social interactions and every-day lives. Investigation of illness experiences were conducted through the use of semi-structured interviews which explored diagnosis experiences, gendered experiences, and life style impact. Significant findings of this research indicated that there are gendered diagnosis experiences among women and men who are diagnosed with this disease. More specifically, female participants reported diagnosis experiences similar to that of a contested illness. In contrast, male participants reported diagnosis experiences that reflect a routinely defined illness. Despite these results, additional research is necessary in order to better understand gendered experiences among those who are diagnosed with Celiac Disease as an adult.

Celiac disease (CD) is an autoimmune disorder that affects approximately 1% of the population [55]. CD is characterized by intestinal villus atrophy after consumption of gluten from wheat, barley, or rye. Patients with CD often experience abdominal pain, diarrhea, malnutrition, fatigue, and a failure to thrive. There is currently no treatment for CD. Patients must live on a strict lifelong exclusion of dietary gluten. Due to the high content of gluten in western diets and poor labeling of gluten content, adherence to a gluten free diet (GFD) is difficult [15].Nearly all the enzymes that can digest the gluten peptide are sensitive to the stomach's low pH . As a result, dietary supplementation with enzymes to digest gluten has yet to produce a viable alternative treatment to a GFD. We propose to use a resident microbe of the human intestinal tract to express a peptidase to digest the immunoreactive gluten fragments. The bacteria, L. reuteri, will colonize the host's intestines and digest the gluten peptides before causing an autoimmune response. To accomplish this task, this thesis describes a food grade, plasmid based system to integrate genes into the genome of L. reuteri. The plasmid system utilizes an origin of replication that requires a protein, RepA, to propagate itself. A helper plasmid provides the RepA protein in trans to an integration plasmid that cannot provide RepA to itself. The integration plasmid carries a homologous region to the genome of L. reuteri allowing for targeted genomic integration. The integration plasmid will not replicate on its own, and will be integrated into the genome if the helper plasmid is absent. To select for these genomic integrants the integration plasmid expresses an erythromycin resistance marker. Using the Cre/Lox system the antibiotic resistance will be removed from the bacterial genome to re-establish the L. reuteri's food grade status. This thesis describes the construction and verification of the above mentioned plasmid tool kit containing the helper, integration, and Cre expression plasmids to integrate genes into the L. reuteri genome.

The gastrointestinal tract specializes in digestion and nutrient absorption via its mucosal surface. Through this large mucosal surface, interactions between the host and its environment, including food antigens and microbes, occur. Therefore, it is imperative that the gut discriminates between innocuous food components, and potential threats such as infections. On some occasions, this fine-tuned discrimination fails, leading to chronic inflammation. Celiac disease (CeD) is an autoimmune enteropathy triggered by gluten, the name given to a family of storage proteins (prolamins) that are naturally found in wheat, barley, and rye. To develop CeD, an individual must carry the susceptibility genes, the HLA-DQ2 and/or HLA-DQ8 alleles and consume gluten. However, this is not sufficient to cause disease, indicating that environmental co-factors are at play. Individuals homozygous for the HLA-DQ2 allele are at high risk to developing CeD in infancy. Currently, there is no existing transgenic animal model that addresses early life exposure to gluten, co-factors, and their effects on CeD development. Therefore, the overall goal of my thesis is to characterize a mouse model transgenic for the HLA-DQ2 allele with exposure to gluten in early life. I first studied the physiological and immunological responses to gluten at the time of solid food introduction using DR3-DQ2 transgenic mice. I determined that after sensitization to gluten before weaning, mice developed moderate enteropathy and some developed both anti-tissue transglutaminase 2 and anti-gliadin antibodies. I then evaluated the recovery of gluten immunopathology after gluten was removed for an extended period. After 6 months on gluten-free food, enteropathy and intestinal anti-gliadin and anti-TG2 antibody levels improved. These findings show pre-weaning sensitization of DR3-DQ2 transgenic mice reproduces key features of CeD, which can be used in future studies to assess environmental triggers and mechanisms that are of importance during early life. / Thesis / Master of Science in Medical Sciences (MSMS) / Celiac disease is the destruction of the upper gut lining by an immune reaction caused by gluten in people with genetic risk. Celiac patients cannot absorb nutrients well and have many complications. While it can occur at any age, its onset in children is associated with the HLA-DQ2 gene. Because not every child with the HLA-DQ2 gene will develop celiac disease, additional factors are suspected. Understanding these factors could help prevent disease, as the only treatment – a life-long gluten-free diet – is not always effective. Thus, an animal model that mimics early life disease onset would be useful. Therefore, I characterized signs of celiac disease in young mice with the HLA-DQ2 gene. I determined that gluten and a microbial toxin given in early life induces inflammation and positive celiac blood tests. This model constitutes a useful tool to test the role of environmental factors in celiac disease in early life.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2006. / Härtill 4 uppsatser.

This thesis is focused on catering for pupils with celiac disease in school canteens. The first part, the theoretical one, deals with the disease itself; it gives basic information about the disease, its history, main symptoms, anatomy of healthy digestive system, and the most common health problems occurring when suffering from celiac disease. At the end of the theoretical part diagnosis of the disease is described as well as suitable and unsuitable diet food for celiac and food legislation. The practical part is a survey focused on catering for pupils with celiac disease at selected elementary schools. The survey was conducted in two regions in Valašské Meziříčí and in Prague. In the final part of my thesis special gluten-free menus for schools are suggested. The pedagogical outcome of my thesis is a lecture on celiac disease which can be held at elementary school s to help pupils find out basic information about this disease.

Celiac disease is an autoimmune disease which occurs in susceptible individuals after ingestion of food containing gluten. Gluten and its monomeric fraction gliadin induce inflammatory damage of the small intestine by activating the immune cells that react strongly to gluten peptides. Gluten peptides have the ability to activate cells of adaptive as well as innate immune system. This work is focused on the production of interleukin (IL)-1 in antigen presenting cells stimulated with peptic gliadin digest. We found that monocytes and peripheral blood mononuclear cells (PBMC) isolated from blood of celiac patients secrete significantly more IL-1α and IL-1β than cells of healthy donors after stimulation with gliadin digest. The gliadin-induced IL-1β expression is controlled by a signaling cascade that includes MAPK kinase family molecules and transcription factor NF-κB. Moreover, we found that the adaptor proteins MyD88 and TRIF as well as Toll-like receptor (TLR) 2 and 4 play a role in the signaling cascade underlying gliadin-induced IL-1β expression by using murine bone marrow derived dendritic cells (BMDC). The precursor form of IL-1β in gliadin- stimulated PBMC and murine BMDC is maturated by caspase-1. In celiac PBMC the gliadin- induced maturation and secretion of IL-1β depends on the potassium...