Z Gastroenterol 2011; 49 - P101
DOI: 10.1055/s-0031-1285373

Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid dendritic cells from patients with Crohn's disease and ulcerative colitis

S Thomas 1, D Metzke 2, J Schmitz 3, Y Dörffel 4, A Radbruch 5, DC Baumgart 1
  • 1Charité – Campus Virchow Klinikum, Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Berlin, Germany
  • 2Charité – Campus Virchow Klinikum, Berlin, Germany
  • 3Miltenyi Biotec, Department of Researh and Development, Berlin, Germany
  • 4Charité – Campus Mitte, Berlin, Germany
  • 5Deutsches Rheumaforschungszentrum, Berlin, Germany

Background: Saccharomyces boulardii (Sb) is probiotic yeast that has demonstrated efficacy in pilot studies in patients with inflammatory bowel disease (IBD). Microbial antigen handling by dendritic cells (DC) is believed to be of critical importance for immunity and tolerance in IBD.

Aim: To characterize the effects of Sb on DC from IBD patients.

Methods: Highly purified (>95%), lipopolysaccharide (LPS) primed CD1c+CD11c+CD123- myeloid DC (mDC) from patients with ulcerative colitis (UC n=26), Crohn's disease (CD n=36) or infectious controls were cultured in the presence or absence of fungal supernatant from Sb (SbS). Phenotype and cytokine production and/or secretion of IBD mDC were measured by flowcytometry and cytometric bead arrays, respectively. T-cell phenotype and proliferation were assessed in a mixed lymphocyte reaction (MLR) with allogenic CD3+CD4+CD45RA+ naïve T-cells from healthy donors. Mucosal healing was investigated in epithelial wounding and migration assays with T-84 cells.

Results: SbS significantly decreased the frequency of CD40, CD80 and CD197 (CCR7) expressing IBD mDC and reduced their secretion of TNF-α and IL-6, while increasing IL-8. In the MLR, SbS significantly inhibited T-cell proliferation induced by IBD mDC. Moreover, SbS inhibited TH1 (TNF-α and IFN-γ) polarization induced by UC mDC and promoted IL-8 and TGF-β dependent mucosal healing.

Conclusion: In summary, we provide novel evidence of synergistic mechanisms how Sb controls inflammation (inhibition of T-cell co-stimulation and inflammation associated migration and mobilization of dendritic cells) and promotes epithelial restitution relevant in IBD. Since the Sb's effects were most prominent in UC mDC, clinical trials in UC seem warranted.