Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.

• Klíčová slova
• T cells, antibodies, biomarkers, gut barrier, inflammatory bowel disease, microbiota,
• MeSH
• biologické markery krev   MeSH
• Crohnova nemoc komplikace   diagnóza   metabolismus   MeSH
• dospělí MeSH
• dysbióza komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sklerozující cholangitida komplikace   MeSH
• ulcerózní kolitida komplikace   diagnóza   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH

Germ-free animals have been used to define the vital role of commensal bacteria on the maturation of the host immune system. However, the role of bacterial residues in diet in this setting is poorly understood. Here we investigated the effect of bacterial contamination in sterile diet on the level of allergic sensitization in germ-free mice. Sterile grain-based diets ST1 and R03 were tested for the level of bacterial contamination. ST1 contained higher amount of bacterial DNA, approximately ten times more endotoxin, and induced higher, TLR4-dependent, cytokine production in dendritic cells compared to R03. In a germ-free mouse model of sensitization to the major birch pollen allergen Bet v 1, feeding on ST1 for at least two generations was associated with decreased production of allergen-specific IgE and IgG1 antibodies in sera in comparison to R03. Furthermore, reduced levels of allergen-specific and ConA-induced cytokines IL-4, IL-5 and IL-13 accompanied by increased levels of IFN-γ were detected in splenocytes cultures of these mice. Our results show that contamination of experimental diet with bacterial residues, such as endotoxin, significantly affects the development of allergic sensitization in germ-free mice. Therefore, careful selection of sterile food is critical for the outcomes of germ-free or gnotobiotic experimental models of immune-deviated diseases.

• MeSH
• alergie imunologie   patologie   MeSH
• antigeny rostlinné imunologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• chov MeSH
• cytokiny biosyntéza   MeSH
• dendritické buňky účinky léků   MeSH
• dieta * MeSH
• DNA bakterií analýza   MeSH
• endotoxiny toxicita   MeSH
• epitopy imunologie   MeSH
• gnotobiologické modely MeSH
• HEK293 buňky MeSH
• imunizace * MeSH
• imunoglobulin A imunologie   MeSH
• imunoglobulin G imunologie   MeSH
• kontaminace DNA MeSH
• kultivované buňky MeSH
• lidé MeSH
• ligandy MeSH
• mitogeny farmakologie   MeSH
• myši inbrední BALB C MeSH
• slezina patologie   MeSH
• toll-like receptor 4 metabolismus   MeSH
• trávicí systém imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny rostlinné MeSH
• Bet v 1 allergen, Betula MeSH Prohlížeč
• cytokiny MeSH
• DNA bakterií MeSH
• endotoxiny MeSH
• epitopy MeSH
• imunoglobulin A MeSH
• imunoglobulin G MeSH
• ligandy MeSH
• mitogeny MeSH
• toll-like receptor 4 MeSH