The dietary polysaccharide from Ommastrephes bartrami prevents chemotherapeutic mucositis by promoting the gene expression of antimicrobial peptides in Paneth cells

Gastrointestinal mucositis (GIM), induced by chemotherapy, is associated with alterations in the function of the intestinal barrier due to the potential damage induced by anti-cancer drugs on the epithelial cells. The Paneth cells, an important epithelial lineage in the intestine, contribute to the innate immunity by releasing antimicrobial proteins onto the mucosal surfaces. Polysaccharide, as a widely used immunomodulatory nutrient, was reported to have an effect of modulating the intestinal immune system. However, the effect of dietary polysaccharides in protecting the Paneth cells from injuries induced by chemotherapy was poorly investigated. In the current study, with a mouse model of cyclophosphamide (Cy)-induced gastrointestinal injury, the polysaccharide extracted from the ink of Ommastrephes bartrami (OBP) were found to protect the mouse Paneth cells from chemotherapeutic injury. Ommastrephes bartrami polysaccharide (OBP) treatment could enhance the mRNA expression of antimicrobial proteins in the Paneth cells, such as lysozyme, Ang4, Defa-5, and sPLA2. The increased production of the microbicidal proteins in the Paneth cells was dependent on the relatively highly developed endoplasmic reticulum (ER) structure but was not dependent on the increase in the quantity of the ER. The Ommastrephes bartrami polysaccharide (OBP) activated the IRE-1 mediated XBP-1s pathway to cope with antimicrobial protein secretion. Our results may have important implications with regard to the role of OBP in chemotherapy-induced Paneth cell injury in intestinal disorders involving inflammation and infection.