This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The probiotic yeast Saccharomyces boulardii ameliorates intestinal injury and inflammation caused by a wide variety of enteric pathogens. We found that Saccharomyces boulardii exerts an anti-inflammatory effect by producing a low molecular weight soluble factor SAIF (S. boulardii anti-inflammatory factor) that blocks MAPK and NF-kB activation and IL-8 gene expression mediated by both pathways in intestinal epithelial cells and monocytes. Partially purified SAIF results in a marked inhibition in the C. difficile toxin-induced enteritis model. We found that this factor is heat-stable, water-soluble and proteinase-insensitive, but glycosidases and aryl-sulfatase senstive. More recently by ion-exchange, we found that SAIF is negatively charged. Simple ion exchange can give 100-fold purification of SAIF. P2 Gel sizing filtration gave us further 20-fold purification and separation of the SAIF fraction. The possible size of SAIF is between 1-2 saccharides. Mass spectrometry of the semi-purified SAIF yielded multiple peaks indicative of saccharides, but indicated that the peak is made up of multiple components. Based on these results, further purification steps are underway. Inhibition of NF-kB activation is an attractive therapeutic target in a wide range of human diseases such as arthritis, asthma and inflammatory bowel disease as well as cancer. As Saccharomyces boulardii has been widely used as probiotics in Europe for decades and now in the U.S., SAIF could be an attractive and safe pharmacologic agent.
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