Development of probiotics with antioxidant action for treatment of inflammatory bowel disease

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1. We investigated the significance of thioredoxin in patients with inflammatory bowel disease (IBD) and found that serum thioredoxin and macrophage migration inhibitory factor (MIF) levels were significantly higher in patients1 with the IBD than normal controls. Serum thioredoxin levels correlated with disease activity.2. Thioredoxin ameliorated dextran sulfate sodium (DSS)-induced colitis and colonic inflammation of interleukin 10 knockout mice. Increase of tumor necrosis factor-α and interferon-γ in colonic tissues was significantly suppressed in thioredoxin-treated mice. Anti-thioredoxin treatment exacerbated DSS-induced colitis with increase of MIF. Recombinant thioredoxin suppressed MIF production in human monocyte cells in in vitro cell culture. Therefore, we speculated that thioredoxin ameliorates colonic inflammation not only by its antioxidative and anti-inflammatory effects but also down-regulating MIF production.3. As thioredoxin administration was effective for the treatment of experimental colitis, we aimed to develop probiotics that secrete thioredoxin because probiotics with antioxidant action is expected to be more beneficial than antioxidant drugs or probiotics alone due to the dual action of scavengery of reactive oxygen species and modulation of intestinal flora. We constructed a thioredoxin expression plasmid and transfected it into Lactobacillus Lactis, which secreted thioredoxin into the culture media. However, administration of thioredoxin-secreting Lactobacillus did not significantly improve experimental colitis, possibly due to low thioredoxin production in the intestine. We are now developing another probiotics which efficiently produces thioredoxin.