Introdução: Bactérias intestinais influenciam a resposta imune e conhecendo-se as ações imunomoduladoras da vitamina D passou-se a investigar sua relação com a microbiota. O status adequado desta vitamina está associado a uma composição mais saudável da microbiota, enquanto sua deficiência pode acarretar disbiose intestinal, endotoxemia, inflamação e resistência à insulina. O conhecimento de interações do status de vitamina D com a microbiota pode melhorar a compreensão da gênese de doenças crônicas mediadas pela inflamação. Objetivo: Examinou-se a associação da ingestão e concentração de vitamina D com a composição da microbiota fecal, marcadores inflamatórios e perfil bioquímico de participantes do Nutritionists Health Study. Métodos: Nesta análise transversal, 150 adultos jovens foram estratificados em tercis de consumo e de concentração de 25(OH)D e comparados quanto ao perfil clínico e inflamatório. A associação de 25(OH)D com a microbiota (sequenciamento do 16S rRNA, região V4, Illumina® MiSeq) foi testada por regressão linear múltipla. Resultados: A ingestão de vitamina D se associou aos níveis séricos (p < 0,05). Não foram observadas diferenças significantes de variáveis clínicas e inflamatórias entre os tercis de ingestão, exceto tendência de aumento do LPS com a redução da 25(OH)D (p-trend < 0,05). Prevotella foi mais abundante (log2FC 1,67; p < 0,01), e Haemophilus and Veillonella menos abundantes (log2FC -2,92 e -1,46; p < 0,01, respectivamente) no subgrupo com maior ingestão de vitamina D (referência) comparado aos outros grupos (primeiro e segundo tercis). PCR (r = -0,170; p = 0,039), selectina-E (r = -0,220; p = 0,007) e abundância de Coprococcus (r = -0,215; p = 0,008) e de Bifdobacterium (r = -0,269; p = 0,001) foram inversamente correlacionados com 25(OH)D. Após ajustes por idade, sexo, estação do ano e IMC, a 25(OH)D manteve associação inversa com Coprococcus ( = -9,414; p = 0,045) e Bifdobacterium ( = -1,881; p = 0,051), mas a significância desapareceu com a adição de marcadores inflamatórios aos modelos. Conclusão: Associações de ingestão e concentração de vitamina D com abundância de certos gêneros da microbiota sugerem que sua ação imunomoduladora poderia influenciar a composição bacteriana. Abundância relativamente maior de gram-negativos (Haemophilus e Veillonella) pode ter sido facilitada pela baixa ingestão e/ou concentração da vitamina. Menor proporção de bactérias benéficas (Coprococcus e Bifidobacterium) poderia estimular a resposta imune e inflamação. Concluímos que a participação da vitamina D na manutenção da homeostase imune deve ocorrer em parte pelas interações com a microbiota intestinal, embora o delineamento transversal impeça assegurar relações tipo causa-efeito. / Introduction: Gut bacteria influence the immune response and due the immunomodulatory actions of vitamin D, it has been investigated its relationship with the microbiota. Adequate status of this vitamin is associated with adequate composition of the microbiota, while its deficiency can cause gut dysbiosis, endotoxemia, inflammation and insulin resistance. The knowledge of interactions of vitamin D status with the microbiota may improve the understanding of the genesis of inflammation-mediated chronic diseases. Objective: We examined the association of vitamin D intake and concentration with the composition of fecal microbiota, inflammatory markers and biochemical profile of participants from the Nutritionists\' Health Study. Methods: In this cross-sectional analysis, 150 healthy young adults were stratified into tertiles of intake and concentrations of vitamin D and their clinical and inflammatory profiles were compared. The association between 25(OH)D and fecal microbiota (16S rRNA sequencing, V4 region, Illumina® MiSeq) was tested by multiple linear regression.) Results: Vitamin D intake was associated with its concentration (p<0.05). There were no significant differences in clinical and inflammatory variables across tertiles of intake, except for a trend of LPS increases with reduction of 25(OH)D (p-trend <0.05). Prevotella was more abundant (log2FC 1.67; p <0.01), and Haemophilus and Veillonella less abundant (log2FC -2,92 e -1.46; p <0.01, respectively) in subset with the highest vitamin D intake (reference) than that observed in the other subset (first plus second tertiles). CRP (r=-0.170, p=0.039), E-selectin (r=-0.220, p=0.007) and abundances of Coprococcus (r=-0.215, p=0.008) and Bifdobacterium (r=-0.269, p=0.001) were inversely correlated with 25(OH)D. After adjusting for age, sex, season and BMI, the 25(OH)D maintained inversely associated with Coprococcus (=-9.414, p=0.045) and Bifdobacterium (=-1.881, p=0.051), but significance disappeared following the addition of inflammatory markers in the regression models. Conclusion: Association of vitamin D intake and concentration with abundance of certain genera of microbiota suggests that its immunomodulatory action could influence the bacterial composition. Relatively higher abundance of gram-negative (Haemophilus and Veillonella) may have been facilitated by the low intake and/or concentration of the vitamin. Lower proportion of beneficial bacteria (Coprococcus and Bifidobacterium) could stimulate the immune response and inflammation. We conclude that the role of vitamin D in maintaining immune homeostasis should occur in part by interactions with the gut microbiota, although the cross-sectional design does not allow ensuring cause-effect relationships.

Research into the gut microbiome has revealed the widespread influence that microbial species have on their host. Host genetics and environmental factors influence the abundance and diversity of the bacterial species living within the gastrointestinal tract. When the normal composition of the gut microbiota is altered, a dysbiotic state incurs. Inflammatory bowel disease (IBD) is a chronic/relapsing inflammatory disorder of the intestinal mucosa, which is characterized by a state of dysbiosis. Despite the large amount of information studying the role dysbiosis has in the pathogenesis of IBD, it is not clear how the altered microbial composition of the gut in IBD patients leads to susceptibility to enteric pathogens such as Clostridium difficile. This study aims to highlight the features of the gastrointestinal tract that are modified as a result of dysbiosis in the IBD population, and how these features facilitate colonization by C. difficile and symptom development. Review of the available literature demonstrated that the depletion of Clostridial cluster XIVa in IBD-associated dysbiosis alters bile acid metabolism and butyrate fermentation in the colon, ultimately promoting germination of C. difficile spores and weakening the gut's immune response against toxin-mediated inflammation. From continued research into the gut microbiota, more will be understood of how these microbial organisms influence human health and disease.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-11-07T17:34:33Z No. of bitstreams: 1 HenriqueCesarTeixeiraVerasDissertacao2013.pdf: 26147875 bytes, checksum: 3014f6ec0d791f46e4e1ee8c49894c2f (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-11-07T17:35:09Z (GMT) No. of bitstreams: 1 HenriqueCesarTeixeiraVerasDissertacao2013.pdf: 26147875 bytes, checksum: 3014f6ec0d791f46e4e1ee8c49894c2f (MD5) / Made available in DSpace on 2018-11-07T17:35:09Z (GMT). No. of bitstreams: 1 HenriqueCesarTeixeiraVerasDissertacao2013.pdf: 26147875 bytes, checksum: 3014f6ec0d791f46e4e1ee8c49894c2f (MD5) Previous issue date: 2013-09-06 / Humans live in constant association with microorganims. The amount of microorganims present in the human body exceeds our own cell number. That community of microorganisms has deep influence in health and disease. The use of high-throughput DNA sequencing technologies and culture independent approaches have been enlarging the understanding concerning the communities of microorganisms and the association of these with the host. The human gastrointestinal tract contains one of the most complex bacterial communities. It was proposed recently that the microbiome can be classified in three enterotypes. In our study, we used data metagenomics quantitative search to identify phylogenetic patterns in the intestinal microbiome to develop prediction models for the enterotypes. To reach this aim, statistical tests were applied to the data regarding abundance of bacteria in level taxonomic corresponding to genus. We identified genus significantly with the abundance different and important correlations. Besides the ratio among genus to be used as parameter bioindicator of the respectives enterotypes. Through the logistic regression test we identified that the prediction model for ET1 was influenced significantly by the ratio of Bacteroides / (Prevotella + Ruminococcus). In the model for prediction of ET2, it was the ratio of Prevotella / Bacteroides with such as characteristic significance. And for the model of ET3, we identified the ratio of (Akkermansia + Alistipes) / (Bacteroides + Prevotella) as significant parameter. These models were assessed against two groups of independent data and associated with the value of cut-off 5%; 20% and 95% respectively. Besides the value of cutoff for each models, the crossed validation allowed the association of the model with the measures of PPV for ET1, specificity for ET2 and PNV for ET3. We propose the experimental validation of these models for the qPCR technique. And with that methodology established, it would be possible to do the diagnosis of the enterotype individually. / Humanos vivem em constante associação com microrganismos. A quantidade de microrganismos presentes no corpo humano ultrapassa o nosso próprio número de células. Essa comunidade de microrganismos tem profunda influência na saúde e doenças. As tecnologias de sequenciamento de DNA de alta capacidade e abordagens moleculares independente de cultura têm ampliado a compreensão acerca das comunidades de microrganismos e a associação destes com o hospedeiro. O trato gastrointestinal humano abriga uma das mais complexas comunidades bacterianas. Foi proposto recentemente que o microbioma pode ser categorizado em três enterotipos. No nosso estudo, utilizamos dados metagenômicos quantitativos buncando identificar padrões filogenéticos no microbioma intestinal para desenvolver modelos de predição para os enterotipos. Para alcançar este objetivo, testes estatísticos foram aplicados aos dados referente a abundância de bactérias em nível taxonômico correspondente a gênero. Identificamos gêneros com a abundância significativamente diferente e correlações importantes. Além da razão entre gêneros para ser utilizada como parâmetro bioindicativo dos respectivos enterotipos. Através do teste de regressão logística identificamos que o modelo de predição para o ET1 foi influenciado significativamente pela razão de Bacteroides / (Prevotella + Ruminococcus). No modelo para predição do ET2, foi a razão de Prevotella / Bacteroides que apresentou significância. E para o modelo do ET3, identificamos a razão de (Akkermansia + Alistipes) / (Bacteroides + Prevotella) como parâmetro significativo. Estes modelos foram avaliados contra dois conjuntos de dados independentes e associados com o valor de cut-off 5%; 20% e; 95% respectivamente. Além do valor de cut-off para cada modelos, a validação cruzada permitiu a associação do modelo com as medidas de PPV para o ET1, especificidade para o ET2 e PNV para o ET3. Propomos a validação experimental destes modelos pela técnica de qPCR. E com essa metodologia estabelecida, seria possível fazer o diagnóstico do enterotipo individualmente.

De nos jours, le changement de style de vie et la consommation excessive d'aliments riches en énergie sont associés avec l'augmentation majeure de l'incidence des maladies métaboliques comme l'obésité et le diabète de type 2. Le diabète de type 2 est caractérisé, entre autre, par une augmentation de la production hépatique de glucose responsable d'une hyperglycémie chronique. Durant ces 10 dernières années, plusieurs études ont suggéré que le microbiote intestinal pouvait être impliqué dans le développement des maladies métaboliques. Le microbiote intestinal est composé de plusieurs milliards de bactéries réparties en plus de 1000 espèces différentes qui colonisent le tractus digestif. Plusieurs études ont montré que certaines pathologies comme le diabète et l'obésité sont caractérisées par des altérations taxonomiques et fonctionnelles du microbiote intestinal. De plus, la colonisation de souris axéniques (i.e. dépourvues de microbiote) par un microbiote intestinal provenant de souris ou d'Hommes obèses/diabétiques est suffisante pour induire la pathologie. Ces résultats suggèrent que les modifications du microbiote intestinal retrouvées chez les patients obèses/diabétiques sont potentiellement impliquées dans le développement des maladies métaboliques. Cependant, l'absence de microbiote intestinal chez les souris axéniques induit des altérations structurelles et fonctionnelles de l'intestin comme une hyperperméabilité intestinale ou un système immunitaire atrophié. Dans ces conditions, il est possible de se demander si les effets délétères induits par la colonisation des souris axéniques avec un microbiote modifié peuvent être observés chez des souris conventionnelles. Pour répondre à cette question nous avons développé un nouveau protocole de transfert de microbiote intestinal dans un modèle de souris conventionnelles. Nous avons transféré le microbiote contenu dans le caecum de souris obèses (" microbiote obèse ") et celui contenu dans le caecum de souris minces (" microbiote mince ") dans des souris conventionnelles non traitées aux antibiotiques. De manière surprenante, le transfert du " microbiote obèse " a induit une diminution de la glycémie à jeun associée à une baisse de la néoglucogenèse hépatique chez les souris transplantées. A l'inverse, le transfert du " microbiote mince " n'a pas modifié la néoglucogenèse. De plus, le transfert du " microbiote obèse " a induit des modifications taxonomiques et fonctionnelles du microbiote intestinal des souris transplantées. De manière intéressante, une fois nourries avec un régime hyperlipidique les souris ayant reçu le " microbiote obèse " ont conservé une glycémie à jeun plus faible que les souris non transplantées. Encore une fois, ce phénotype résulte d'une diminution de la production hépatique de glucose caractérisée par une baisse de l'activité des enzymes néoglucogéniques phosphoenolpyruvate carboxykinase et glucose-6-phosphatase. Par ailleurs, ces souris sont également moins grasses que les souris non transplantées. En conclusion, nous avons montré que le transfert d'un " microbiote obèse " peut moduler le métabolisme hépatique et prévenir l'augmentation de la néoglucogenèse hépatique normalement induite par le régime hyperlipidique chez des souris conventionnelles. Ces travaux de thèse ont montré d'une part, que la modification du microbiote intestinal de souris conventionnelles est possible par transfert de microbiote caecal. D'autre part et contre toutes attentes, ces résultats mettent en lumière que, contrairement aux observations faites chez les souris axéniques, le transfert d'un " microbiote obèse " dans une souris conventionnelle n'induit pas les phénotypes caractéristiques des maladies métaboliques. Par ailleurs, ce modèle de transfert caecal pourrait être utile pour la compréhension du rôle des bactéries intestinales sur le développement des maladies métaboliques. / Nowadays, the change of lifestyle and increase in the consumption of high-calorie foods are associated with a marked rise of the prevalence of metabolic diseases, including obesity and type 2 diabetes. Type 2 diabetes is linked, at least in part, to an increase of hepatic glucose production responsible for a fasting hyperglycemia. In the past decade, an increasing body of evidence has proposed gut microbiota as a new factor contributing to these metabolic alterations. Gut microbiota consists of trillions of bacteria identifying more than 1000 different species that inhabit our intestine. A body of work has demonstrated that multiple pathologies such as type 2 diabetes and obesity are characterized by an altered proportion and activity of the gut microbiota. In addition, the colonization of germ-free mice with the gut microbiota from either obese/diabetic humans or obese/diabetic mice transfers the phenotype. These results suggest that the modifications of the gut microbiota found in obese/diabetic patients are a potential etiologic factor for those diseases. Nevertheless, the lack of microbiota in germ-free mice determines both structural and functional alterations such as gut hyperpermeability and the atrophy of the immune system. Therefore, we could wonder whether the detrimental effects of the gut microbiota from obese/diabetic patients observed in germ-free mice may also be observed in healthy conventional mice. To address this issue, we have developed a new gut microbiota transferring process from conventional mice to other mice. We have transferred the cecal microbiota harvested from either obese ("obese microbiota") or lean ("lean microbiota") mice in antibiotic-free conventional mice. Surprisingly, the mice which received the "obese microbiota" had a reduced fasted glycaemia compared to the mice which received the "lean microbiota". This diminution could be attributed to a decrease of the hepatic gluconeogenesis since conversion from pyruvate to glucose and phosphoenolpyruvate carboxykinase activity were lower in the liver of mice which received the "obese microbiota". Conversely, the transfer of the "lean microbiota" did not affect the hepatic gluconeogenesis. In addition, the transfer of the "obese microbiota" changed gut microbiota composition and the microbiome of recipient mice. Interestingly, mice which received the "obese microbiota" and fed a high-fat diet still exhibited reduced fed and fasted glycaemia. Once again, this phenotype was due to a decrease of hepatic gluconeogenesis characterized by a diminution of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activity. In addition, the mice which received the "obese microbiota" had less adiposity compared to the non-transferred mice. Finally, we reported that transferring the "obese microbiota" impact on hepatic metabolism and prevent HFD-increase hepatic gluconeogenesis. On the one hand, these thesis works, have demonstrated that it is possible to modify the gut microbiota by our caecal transferring process. On the other hand, our results suggest that the transfer of the "obese microbiota" in conventional mice does not induced some characteristics of metabolic diseases contrary to that it is observed in germ-free mice. Furthermore, this kind of gut microbiota transferring process may be useful for a better understanding of the etiology of metabolic diseases.

Acteur clé de la symbiose hôte-microbiote, les IgA sécrétoires modulent le microbiote et participe à l'homéostasie intestinale. Chez la souris, les IgA sont polyréactives, en reconnaissent diverses bactéries, elles régulent la composition du microbiote et réduisent l'inflammation intestinale. Ces observations ouvrent des perspectives thérapeutiques intéressantes. Cependant, les caractéristiques des IgA et leurs spécificités restent mal connues chez l'homme. L'objectif de ce travail a donc été d'étudier la spécificité de la réponse IgA, en distinguant IgA1 et IgA2. La mise au point d'une technique de production in vitro d'IgA monoclonales 100% humaines issues de l'intestin nous a permis de montrer le profil de polyréactivité des IgA. Chaque IgA interagit avec un spectre large mais défini de bactéries commensales. Par ailleurs, les IgA1 et les IgA2 ciblent la même fraction du microbiote. Les réponses IgA1 et IgA2 convergent aussi au niveau des épitopes polysaccharidiques reconnus. Si les IgA sécrétoires contribuent largement à l’homéostasie intestinale, des IgG sériques anti-microbiote jouent un rôle dans la relation symbiotique hôte-microbiote. Leur présence n’ayant pas encore été démontrée chez l’homme en condition physiologique, ce travail a eu pour objectif secondaire de les explorer. Le développement d’une technique de cytométrie bactérienne nous a permis de détecter des IgG ciblant les bactéries commensales dans le sérum des individus sains. Ces IgG anti-microbiote sont dirigées vers les bactéries déjà reconnues par les IgA sécrétoires, elles présentent des spécificités propres à chaque individu. / IgA, the dominant immunoglobulin produced in the gut, plays diverse roles ranging from toxin neutralization, immune functions regulation, intestinal homeostasis maintenance. It is now well established that polyreactive IgA, which target multiple bacteria, can modulate gut microbiota composition and have promising therapeutic effects. However, IgA features remain elusive in humans. We therefore determined the reactivity profile of native monoclonal antibodies from human colon and compared IgA1 and IgA2. We found that IgA are polyreactive and bind a diverse but restricted subset of gut commensals. Most commensals were dually coated by IgA1 and IgA2, yet IgA2 alone coated a distinct fraction of colonic bacteria. Besides their common microbial targets, IgA1 and IgA2 exhibited overlapping anti-carbohydrate repertoires. An essential link between IgA and IgG responses against microbiota has been recently demonstrated in mice. Nevertheless, it remains unclear whether symbiotic bacteria could induce systemic IgG under homeostatic conditions in humans. Hence, we characterized anti-microbiota IgG in serum of healthy donors by bacterial flow cytometry. We found that each individual harbored a diverse and private panel of anti-commensals IgG that converge with secretory IgA to cover a restricted fraction of the gut microbiota. Patients with IgA deficiency or common variable immunodeficiency (CVID) exhibited a distinct set of anti-commensals IgG suggesting that IgA replacement in addition to polyvalent IgG might be beneficial to treat gastro-intestinal symptoms in these patients.

Exposure to environmental pollutants poses numerous risk factors for human health, including increasing incidence of cardiovascular disease and diabetes. Persistent organic pollutants, such as polychlorinated biphenyls (PCBs) have been strongly linked to the development of these chronic inflammatory diseases and the primary route of exposure is through consumption of contaminated food products. Thus, the gastrointestinal tract is susceptible to the greatest levels of these pollutants and is an important facet to study. The first two hypotheses of this dissertation tested that exposure to PCBs disrupts gut microbiota directly (in vitro) and within a whole body system. PCB exposure disrupted microbial metabolism and production of metabolites (i.e. short chain fatty acids) in vitro. These disruptions in microbial populations were consistent in our mouse model of cardiometabolic disease, where we observed reductions in microbial diversity, an increase in the putative pro-inflammatory ratio of Firmicutes to Bacteroidetes, and reductions in beneficial microbial populations in exposed mice. Furthermore, observed greater inflammation was observed both within the intestines and peripherally in PCB exposed mice as well as disruptions in circulating markers associated with glucose homeostasis. Nutritional interventions high in prebiotic dietary fiber such as inulin may be able to attenuate the toxic effects of pollutant exposure. To test the hypothesis that consumption of the prebiotic inulin can decrease PCB-induced disruption in gut microbial and metabolic homeostasis, LDLr-\- mice were fed a diet containing inulin and exposed to PCB 126. Mice fed an inulin-containing diet and exposed to PCBs exhibited improved glucose tolerance, lower hepatic inflammation and steatosis, and distinct differences in gut microbial populations. Overall, these data suggests that nutritional intervention, specifically prebiotic consumption, may reduce pollutant-induced disease risk.

Introduction: Diabetes is a global and rapidly increasing disease that in 2014 affected morethan 422 million people, and takes 1,2 million lives per year. The importance of identifyingnew ways to manage and prevent the disease has led science to a new area – modulation ofthe gut microbiota. It is well known that the composition of gut microbiota differs betweennon-diabetic and diabetic adults, and that nutrition is the main way to modulate gutmicrobiota composition. Food and lifestyle are of great importance for the development andtreatment of type 2 diabetes and pre-diabetes, but less is known about whether gut microbiotamodulation is mediating that link. Aim: The aim is to examine whether there is a scientifically well-supported link between diet,gut microbiota and the development or treatment of type 2 diabetes or pre-diabetes in humans. Methods: Systematic review with literature search via PubMed and Cochrane, following themanual from the Swedish Agency for Health Technology Assessment and Assessment ofSocial Services (SBU). Results: Of 12 articles finally included, two studies found a strong impact of diet on diabetesrelatedvariables via modulation of gut microbiota. Another four studies did not find anassociation, and six studies lacked sufficient data to be able to draw a conclusion. Dietinterventions and study design differed between studies, which led to heterogeneous results. Conclusions: This review demonstrates a large knowledge gap in how dietary modificationscan prevent or treat type 2 diabetes or pre-diabetes via changes in gut microbiota.

Vitamin D may have immunomodulatory effects in the intestine. Our objective was to determine if exposure to vitamin D mitigates intestinal inflammation in IL-10 KO mice. Mice were randomized to a diet containing 25 IU (low) or 5000 IU (high) of vitamin D/kg of diet in utero and offspring were maintained on the same diet or switched to the other diet at weaning. Fecal samples were collected at 3 months of age. Vitamin D did not affect intestinal inflammation in male and female mice and did not affect KC cytokine concentration or regulate colonic gene expression in male mice. Vitamin D modulated the gut microbiota in a sex-specific manner and depending on timing of exposure. Females in the HH group had significantly higher fecal counts of C. coccoides than the other vitamin D interventions. Therefore, vitamin D may favourably modulate microbiota composition without attenuating inflammation.

Vitamin D may have immunomodulatory effects in the intestine. Our objective was to determine if exposure to vitamin D mitigates intestinal inflammation in IL-10 KO mice. Mice were randomized to a diet containing 25 IU (low) or 5000 IU (high) of vitamin D/kg of diet in utero and offspring were maintained on the same diet or switched to the other diet at weaning. Fecal samples were collected at 3 months of age. Vitamin D did not affect intestinal inflammation in male and female mice and did not affect KC cytokine concentration or regulate colonic gene expression in male mice. Vitamin D modulated the gut microbiota in a sex-specific manner and depending on timing of exposure. Females in the HH group had significantly higher fecal counts of C. coccoides than the other vitamin D interventions. Therefore, vitamin D may favourably modulate microbiota composition without attenuating inflammation.

Pastaraisiais dešimtmečiais industrinėse, išsivysčiusiose Vakarų Europos ir Šiaurės Amerikos šalyse ypač išaugo lėtinėmis uždegiminėmis žarnų ligomis (UŽL) sergančių vaikų skaičius. UŽL etiopatogenezė nėra pilnai aiški, tačiau manoma, kad jų išsivystymą sąlygoja pakitęs imuninis atsakas į žarnyno bakterijų antigenų stimuliaciją genetiškai predisponuotiems individams. Genetiniai tyrimai parodė genų polimorfizmo reikšmę atpažįstant bakterijas (NOD2) bei jų įtaką tokiuose ląstelės mechanizmuose, kaip imunoreguliacija (IL23R, IL10) bei autofagija (ATG16L1, IRGM). Naujausių tyrimų, atliktų su UŽL sergančiais individais, duomenimis, pakitusi žarnyno bakterijų sudėtis sukelia imuninės sistemos stimuliaciją, epitelio funkcijos sutrikimą bei gleivinės pralaidumą, dėl ko išsivysto lėtinis žarnyno gleivinės uždegimas. Remiantis klinikinių, radiologinių, endoskopinių bei histologinių tyrimų duomenimis, išskiriamos dvi UŽL: opinis kolitas (OK) ir Krono liga (KRL). OK – lėtinis storosios žarnos uždegimas, kurio metu pažeidžiami paviršiniai, t. y. gleivinės ir pogleivio, žarnos sluoksniai. KRL atveju, uždegiminiai pakitimai apima ne tik paviršinius, bet ir giliuosius žarnos sienelės sluoksnius, kurie gali atsirasti bet kurioje žarnyno dalyje, tačiau dažniausiai stebimi plonosios žarnos galinėje bei storosios žarnos pradinėje dalyse. Neseniai atlikti epidemiologiniai tyrimai parodė, kad vaikų, sergančių UŽL, sergamumas ir paplitimas kito: Krono ligos susirgimų atvejų skaičius laipsniškai... [toliau žr. visą tekstą] / In recent decades the number of children with chronic inflammatory intestinal diseases (IBD) has increased in the industrialized developed countries of Western Europe and North America [Benchimol et al., 2011; Molodecky et al., 2012]. IBD pathogenesis is not completely clear, but it is though it evolves from changes in the immune response to antigen stimulation of intestine bacteria to genetically predisposed individuals [Xavier et al., 2008]. Genetic studies have shown the importance of genetic polymorphism in identifying of bacteria (NOD2) and their influence on cell mechanisms such as immune regulation and autophagy (IRGM, ATG16L1) [Travasso et al., 2009; Cooney et al., 2009]. According to the data of the recent studies with IBD, the changed composition of the intestinal bacteria causes immune stimulation, epithelial dysfunction, and mucosal permeability, as a result, chronic inflammation of the intestinal mucosa develops. Based on the data of clinical, radiological, endoscopic and histological studies, there are two IBD subtypes: ulcerative colitis (UC) and Crohn's disease (CD). UC is a chronic inflammation of the large intestine, when surface layers, i.e. mucosa and submucosa are affected. In CD inflammatory changes include not only the surface but also the deeper layers of the intestinal wall, which can occur in any part of the intestine. These changes are often seen in the end of the small intestine and in the initial part of the large intestine. Recent... [to full text]