Long-Chain Polyphosphate Is a Potential Agent for Inducing Mucosal Healing of the Colon in Ulcerative Colitis

The goal of ulcerative colitis (UC) treatment has recently been shown to be "mucosal healing," as no drug directly induces mucosal healing. Probiotics possess sufficient safety, but their efficacy in the treatment of UC remains controversial because of the influence of intestinal conditions. It is believed that the identification of bioactive molecules produced by probiotics and their application will help to solve this issue. We therefore identified a probiotic-derived long-chain polyphosphate as a molecule enhancing the intestinal barrier function. This study demonstrated that long-chain polyphosphate exhibited antiinflammatory effects in a human macrophage and interleukin-10 knockout transfusion mouse model. The first-in-human trial showed that 7 of the 10 enrolled patients acquired clinical remission, 4 of whom achieved endoscopic remission despite a history of treatment with anti-tumor necrosis factor (TNF)-α agents. No adverse reactions were observed. Long-chain polyphosphate might be useful for the treatment of refractory UC, even in patients with failure or intolerance to anti-TNF-α therapy.