Inflammatory bowel disease (IBD) is a group of disorders causing inflammation in the digestive tract. Recent data suggest that dysbiosis may play a pivotal role in the IBD pathogenesis. As microbiome-based therapeutics that modulate the gut ecology have been proposed as a novel strategy for preventing IBD, the aim of presenting study was to evaluate the dextran sulphate sodium (DSS) rat model mainly in terms of microbial shifts to confirm its suitability for dysbiosis study in IBD. Acute colitis was induced using 5% DSS solution for seven days and rats were euthanized five days after DSS removal. The faecal/caecal microbiota was analyzed by next generation sequencing. Disease activity index (DAI) score was evaluated daily. Blood and colon tissue immunophenotyping was assessed by flow cytometry and histological, haematological, and biochemical parameters were also evaluated. The colitis induction was reflected in a significantly higher DAI score and changes in all parameters measured. This study demonstrated significant shifts in the colitis-related microbial species after colitis induction. The characteristic inflammation-associated microbiota could be detected even after a five day-recovery period. Moreover, the DSS-model might contribute to an understanding of the effect of different treatments on extraintestinal organ impairments. The observation that certain bacterial species in the gut microbiota are associated with colitis raises the question of whether these organisms are contributors to, or a consequence of the disease. Despite some limitations, we confirmed the suitability of DSS-induced colitis model to monitor microbial changes during acute colitis, in order to test attractive new microbiome-based therapies.

• Klíčová slova
• DSS-induced colitis, colon cytokines, faecal and caecal microbiota,
• Publikační typ
• časopisecké články MeSH

PURPOSE: Crohn's disease (CD) belongs to chronic disorders with unpredictable disease course. The aim of this study was to identify how genetic testing (NOD2/CARD15) can be used in patients with CD to predict the need for surgical treatment (to define an aggressive type of disease where the patient can profit from early surgery). METHODS: The patients who were tested genetically had undergone a surgery due to CD at the Department of Surgery University Hospital Brno Bohunice between 2010 and 2016. The control group consisted of patients with CD who had been diagnosed with CD at least 5 years prior to the testing and had not required any surgical intervention. The second control group was healthy subjects. RESULTS: In total, there were 117 operated patients for CD, 77 patients with CD that had not undergone surgery for CD and 30 healthy subjects. For patients with at least one genetic mutation, the risk of the necessity of surgical treatment of CD is 1.96 times higher than for patients with no mutation. Patients with two or more mutations were generally operated on at a younger age, in a shorter time after being diagnosed and each patient had a partial resection of the ileum. CONCLUSION: The group of operated patients with CD had a significantly higher distribution of at least one genetic mutation as opposed to the non-operated group. In patients with two or more mutations, the disease course was more aggressive. This group of patients might profit from the conservative top-down or early surgical therapy.

• Klíčová slova
• Crohn’s disease, Czech cohort, Disease course, Genetics, Inflammatory bowel disease, Intestinal resection, NOD2/CARD15, Surgery,
• MeSH
• alely MeSH
• Crohnova nemoc genetika   chirurgie   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace genetika   MeSH
• prognóza MeSH
• rizikové faktory MeSH
• signální adaptorový protein Nod2 genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• NOD2 protein, human MeSH Prohlížeč
• signální adaptorový protein Nod2 MeSH

BACKGROUND: Reduced microbial diversity has been associated with inflammatory bowel disease (IBD) and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis. METHODS: Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)-induced colitis was used to compare their beneficial effects in vivo. RESULTS: The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum. CONCLUSIONS: We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.

• MeSH
• Bifidobacterium klasifikace   fyziologie   MeSH
• dendritické buňky mikrobiologie   patologie   MeSH
• HEK293 buňky MeSH
• imunoenzymatické techniky MeSH
• kolitida chemicky indukované   prevence a kontrola   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• probiotika farmakologie   MeSH
• signální adaptorový protein Nod2 genetika   metabolismus   MeSH
• síran dextranu toxicita   MeSH
• střeva mikrobiologie   patofyziologie   MeSH
• toll-like receptor 2 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• signální adaptorový protein Nod2 MeSH
• síran dextranu MeSH
• Tlr2 protein, mouse MeSH Prohlížeč
• toll-like receptor 2 MeSH

BACKGROUND: The CTLA4 (cytotoxic T-lymphocyte antigen 4) gene is associated with several immunopathologic diseases and because of its important immuno-regulatory role it may be considered also a plausible candidate for a genetic association with inflammatory bowel diseases. Previously published studies found no association of CTLA4 with Crohn's disease itself, but some indicated an association with its subphenotypes. The aim of this study was to assess the association in the Czech population, using a set of markers shown to associate with other diseases. METHODS: Six polymorphisms within the CTLA4 region were investigated in 333 patients with Crohn's disease and 482 unrelated healthy controls, all Caucasians of Czech origin. The genotypes of the SNPs were determined using the TaqMan SNP genotyping assays. Haplotypes were reconstructed using an expectation-maximization algorithm, and their association with the condition was assessed using log-linear modeling. Then, potential interactions were tested between the CTLA4 variants and other genetic factors known to confer the disease susceptibility. RESULTS: No crude associations with Crohn's disease were found for the tested CTLA4 variants under the log-additive or dominant models. However, when stratified for the genetic risk conferred by the variants in the NOD2 (the p.Leu1007fsX1008, rs5743293) or the IL23R (p.R381Q, rs11209026), a significant negative association emerged for the minor alleles of CTLA4 CT60 (rs3087243), JO31 (rs11571302), JO27-1 (rs11571297) polymorphisms. This negative association with CTLA4 was apparent only in the strata defined by presence minor alleles at the NOD2 rs5743293 (here the CTLA4 CT60 A coffered an OR = 0.43, 95%CI 0.19 - 0.95 for the presence of CT60 A), or IL23R rs11209026 (here the OR for presence of CT60 A was 0.23, 95%CI 0.07 - 0.71). We observed this effect also for the haplotype consisting of minor alleles of the three tightly linked CTLA4 markers. Furthermore, this haplotype was associated with the younger age at diagnosis (OR 1.52, 95%CI 1.09 - 2.11, p = 0.014). CONCLUSIONS: A protective effect of a CTLA4 haplotype was unmasked after stratification for the risk variants in the NOD2 and IL23R genes, and may point towards the biological relevance of the molecule in the pathogenesis of the disease.

• MeSH
• alely MeSH
• antigen CTLA-4 MeSH
• běloši genetika   MeSH
• CD antigeny MeSH
• Crohnova nemoc epidemiologie   genetika   MeSH
• cytotoxické T-lymfocyty MeSH
• genotyp MeSH
• haplotypy MeSH
• idiopatické střevní záněty genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• CD antigeny MeSH
• CTLA4 protein, human MeSH Prohlížeč