The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.

• Klíčová slova
• celiac disease, gluten-free diet, immune response, infections, microbiota, parasites,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: Human colostrum and milk provide a newborn with immunomodulatory components, ensuring protection and proper development of the immune system. Secretory IgA antibodies in colostrum represent the first line of defence against harmful substances, but their potential spectra of reactivity with autoantigens remains unclear. Here, we characterised the repertoire of natural sectretory IgA autoantibodies in colostrum of healthy mothers. METHODS: The human colostrum samples from 39 healthy mothers were analyzed for autoantibodies by indirect immunofluorescence, dot blots, immunoblots and ELISA. RESULTS: We found that there is high diversity in reactivities of colostral IgA antibodies to autoantigens among individual samples. Using tissue sections and biochips commonly used for autoimmunity testing, we found that most samples reacted with monkey ovary (79.3%), monkey pancreatic tissue (78.6%), human HEp-2 cells (69%) and monkey adrenal gland (69.0%), fewer samples reacted with monkey liver tissue (47.2%), rat stomach (42.9%), monkey testicular tissue (41.4%), monkey salivary gland (39.3%), rat kidney (32.1%) and monkey cerebellar tissue (17.9%). At the protein level, we detected reactivity of IgA with 21 out of 25 (auto) antigens. The majority of the samples reacted with the pyruvate dehydrogenase complex, E3 ubiquitin ligase, cytosolic liver antigen, promyelocytic leukemia protein and nuclear pore glycoprotein-210. Using ELISA, we found reactivity of colostral IgA antibodies against examined extractable nuclear antigens, double stranded DNA, phospholipids and neutrophil cytoplasm. CONCLUSIONS: The broad spectrum of polyreactive natural autoantibodies present in human colostrum may contribute to proper development of mucosal immune system of the breastfed infant.

• MeSH
• autoantigeny imunologie   metabolismus   MeSH
• autoprotilátky imunologie   metabolismus   MeSH
• dospělí MeSH
• ELISA MeSH
• Haplorrhini MeSH
• imunoglobulin A sekreční biosyntéza   imunologie   MeSH
• imunohistochemie MeSH
• kojenec MeSH
• kojení MeSH
• kolostrum chemie   imunologie   MeSH
• krysa rodu Rattus MeSH
• laktace imunologie   MeSH
• lidé MeSH
• matky MeSH
• mladiství MeSH
• proteiny imunologie   metabolismus   MeSH
• specificita protilátek MeSH
• těhotenství MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mladiství MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH
• imunoglobulin A sekreční MeSH
• proteiny MeSH

Metagenomic approaches are currently being used to decipher the genome of the microbiota (microbiome), and, in parallel, functional studies are being performed to analyze the effects of the microbiota on the host. Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization. Animals used as models of human diseases can be maintained in sterile conditions (isolators used for germ-free rearing) and specifically colonized with defined microbes (including non-cultivable commensal bacteria). The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models. Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia (i.e., using models of human inflammatory bowel disease and colorectal carcinoma). In contrast, a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Interestingly, the development of atherosclerosis in germ-free apolipoprotein E (ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals. Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota. Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial, disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components (e.g., probiotics and prebiotics) whose administration may aid in disease prevention and treatment.

• MeSH
• autoimunitní nemoci etiologie   mikrobiologie   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• gnotobiologické modely * MeSH
• imunita MeSH
• lidé MeSH
• metagenom imunologie   MeSH
• modely nemocí na zvířatech MeSH
• nádory etiologie   mikrobiologie   MeSH
• sliznice imunologie   MeSH
• zánět etiologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND AND AIMS: Celiac disease (CD) is a chronic inflammatory disorder of the small intestine that is induced by dietary wheat gluten proteins (gliadins) in genetically predisposed individuals. The overgrowth of potentially pathogenic bacteria and infections has been suggested to contribute to CD pathogenesis. We aimed to study the effects of gliadin and various intestinal bacterial strains on mucosal barrier integrity, gliadin translocation, and cytokine production. METHODOLOGY/PRINCIPAL FINDINGS: Changes in gut mucosa were assessed in the intestinal loops of inbred Wistar-AVN rats that were reared under germ-free conditions in the presence of various intestinal bacteria (enterobacteria and bifidobacteria isolated from CD patients and healthy children, respectively) and CD-triggering agents (gliadin and IFN-γ) by histology, scanning electron microscopy, immunofluorescence, and a rat cytokine antibody array. Adhesion of the bacterial strains to the IEC-6 rat cell line was evaluated in vitro. Gliadin fragments alone or together with the proinflammatory cytokine interferon (IFN)-γ significantly decreased the number of goblet cells in the small intestine; this effect was more pronounced in the presence of Escherichia coli CBL2 and Shigella CBD8. Shigella CBD8 and IFN-γ induced the highest mucin secretion and greatest impairment in tight junctions and, consequently, translocation of gliadin fragments into the lamina propria. Shigella CBD8 and E. coli CBL2 strongly adhered to IEC-6 epithelial cells. The number of goblet cells in small intestine increased by the simultaneous incubation of Bifidobacterium bifidum IATA-ES2 with gliadin, IFN-γ and enterobacteria. B. bifidum IATA-ES2 also enhanced the production of chemotactic factors and inhibitors of metalloproteinases, which can contribute to gut mucosal protection. CONCLUSIONS: Our results suggest that the composition of the intestinal microbiota affects the permeability of the intestinal mucosa and, consequently, could be involved in the early stages of CD pathogenesis.

• MeSH
• Bacteria patogenita   MeSH
• bakteriální toxiny farmakologie   MeSH
• Bifidobacterium patogenita   MeSH
• celiakie etiologie   MeSH
• cytokiny biosyntéza   MeSH
• Enterobacteriaceae patogenita   MeSH
• gliadin farmakokinetika   farmakologie   MeSH
• gnotobiologické modely MeSH
• interakce hostitele a patogenu účinky léků   MeSH
• interferon gama farmakologie   MeSH
• krysa rodu Rattus MeSH
• permeabilita MeSH
• pohárkové buňky patologie   MeSH
• střeva mikrobiologie   patologie   MeSH
• střevní sliznice účinky léků   metabolismus   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální toxiny MeSH
• cytokiny MeSH
• gliadin MeSH
• interferon gama MeSH

Heat-inactivated Lactobacillus casei LOCK 0900, L. casei LOCK 0908 and Lactobacillus paracasei LOCK 0919 strains, applied to blood cell cultures obtained from children with atopic dermatitis induced production of anti-allergic T(H)1 cytokines (interleukin-12, interleukin-18, interferon-gamma, tumor necrosis factor-alpha) and regulatory transforming growth factor-beta(1)), but did not stimulate pro-allergic interleukin-5. The lactobacilli-mixture remarkably enhanced the T(H)1 response compared to single strains. This synergistic effect was not observed for transforming growth factor-beta(1). In contrast, the amount of interleukin-10 was found to be considerably lower when cells were stimulated with lactobacilli-mixture compared to single strains. The mixture of Lactobacillus strains represents a probiotic bacterial preparation modulating in vitro cytokine profile of allergic children towards anti-allergic T(H)1 response.

• MeSH
• atopická dermatitida imunologie   MeSH
• cytokiny metabolismus   MeSH
• imunologické faktory farmakologie   MeSH
• kojenec MeSH
• kultivované buňky MeSH
• Lactobacillus imunologie   MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé MeSH
• probiotika farmakologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• imunologické faktory MeSH

Intestinal microbiota in exclusively breast-fed infants with blood-streaked stools and in healthy exclusively breast-fed babies was compared. Total anaerobes, bifidobacteria, lactobacilli, coliform bacteria, enterococci and clostridia were quantified by cultivation methods in feces of 17 full-term exclusively breastfed patients (aged 16.3 +/- 7.4 weeks) with blood-streaked stools and in the control group of 22 healthy fullterm exclusively breast-fed infants (13.7 +/- 6.4 weeks). Specific fluorescence in situ hybridization kits for Bifidobacterium spp. were used for the quantitative detection of bifidobacteria in samples. Control samples had significantly (p < 0.05) higher counts of total anaerobes. Bifidobacteria were not detected in patients' samples in 65 % and in controls in 36 % (p < 0.01). Bifidobacteria counts were also significantly higher in the control group (p < 0.01). Furthermore, clostridia strains were detected only in feces from bifidobacteria-negative infants reaching counts >8 log CFU/g. Lactobacilli were not detected in 65 % patients and in 45 % control samples. However, this difference was not significant as well as the difference in lactobacilli counts. Eosinophilia was observed in 35 % of patients, low IgA concentration in 71 % and also low IgG concentration in 71 %. pANCA positivity was found in 53 % of patients. In conclusion a significant low proportion of bifidobacterial microbiota in patients with blood-streaked stools was shown in comparison with controls.

• MeSH
• Bacteria izolace a purifikace   MeSH
• feces mikrobiologie   MeSH
• imunoglobulin A krev   MeSH
• imunoglobulin G krev   MeSH
• kojenec MeSH
• kojení * MeSH
• lidé MeSH
• proktokolitida imunologie   mikrobiologie   MeSH
• střeva mikrobiologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobulin A MeSH
• imunoglobulin G MeSH

Dysregulation of innate and adaptive intestinal immune responses to bacterial microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2), TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon samples were obtained by colonoscopy from patients with Crohn's disease (CD), ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and CD14 showed a significant increase in TLR2 expression in the terminal ileum of patients with inactive and active UC against controls. Significant upregulation of TLR4 expression relative to controls was found in the terminal ileum and rectum of UC patients in remission and in the terminal ileum of CD patients with active disease. CD14 expression was upregulated in the terminal ileum of CD patients in remission and with active disease, in the cecum of UC patients in remission and with active disease, and in rectum of UC patients with active disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.

• MeSH
• biopsie MeSH
• cékum metabolismus   patologie   MeSH
• Crohnova nemoc metabolismus   patologie   MeSH
• ileum metabolismus   patologie   MeSH
• imunohistochemie MeSH
• lidé MeSH
• lipopolysacharidové receptory biosyntéza   MeSH
• rektum metabolismus   patologie   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• toll-like receptor 2 biosyntéza   MeSH
• toll-like receptor 4 biosyntéza   MeSH
• ulcerózní kolitida metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipopolysacharidové receptory MeSH
• TLR2 protein, human MeSH Prohlížeč
• TLR4 protein, human MeSH Prohlížeč
• toll-like receptor 2 MeSH
• toll-like receptor 4 MeSH