Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression

Saccharomyces boulardii (Sb) is a non-pathogenic yeast that ameliorates intestinal injury and inflammation caused by a wide variety of enteric pathogens. We hypothesized that Sb may exert its probiotic effects by modulation of host cell signaling and pro-inflammatory gene expression. Human HT-29 colonocytes and THP-1 monocytes were stimulated with IL-1β, TNFα or LPS in the presence or absence of Sb culture supernatant (SbS). IL-8 protein and mRNA levels were measured by ELISA and RT-PCR, respectively. The effect of SbS on IκBα degradation was studied by Western blotting and on NF-κB-DNA binding by EMSA. NF-κB-regulated gene expression was evaluated by transient transfection of THP-1 cells with a NF-κB-responsive luciferase reporter gene. SbS inhibited IL-8 protein production in IL-1β or TNFα stimulated HT-29 cells (by 75% and 85%, respectively; P < 0.001) and prevented IL-1β-induced up-regulation of IL-8 mRNA. SbS also inhibited IL-8 production, prevented IκBα degradation, and reduced both NF-κB-DNA binding and NF-κB reporter gene up-regulation in IL-1β or LPS-stimulated THP-1 cells. Purification and characterization studies indicate that the S. boulardii anti-inflammatory factor (SAIF) is small (<1 kDa), heat stable, and water soluble. The probiotic yeast Saccharomyces boulardii exerts an anti-inflammatory effect by producing a low molecular weight soluble factor that blocks NF-κB activation and NF-κB-mediated IL-8 gene expression in intestinal epithelial cells and monocytes. SAIF may mediate, at least in part, the beneficial effects of Saccharomyces boulardii in infectious and non-infectious human intestinal disease.