Probiotics, including Lactobacillus and Bifidobacterium, is live microorganisms which, when administered in adequate amounts, confer a health benefit on the host, such as intestinal conditioning and anti-inflammatory effects. However, the intestinal protective molecules derived from probiotic bacteria has been less identified. In this study, we identified inorganic long chain polyphosphate as the intestinal protective molecules from the culture supernatant of Lactobacillus brevis SBC8803 by using HPLC and elemental analysis. Polyphosphate activated integrin β1-p38MAPK signaling pathway and its intestinal protective effect was diminished by the inhibition of epithelial integrin. Polyphosphate was recognized by integrin, incorporated to epithelial cells through endocytic pathway from apical side, and then released to apical side. Polyphosphate improved the intestinal injury in rat DSS induced colitis model and investigator initiated clinical trial targeted to ulcerative colitis patients. Therefore, probiotic derived polyphosphate will be applied for treatment of refractory intestinal bowel disease.