The protective role of Chitooligosaccharides against chronic ulcerative colitis induced by dextran sulfate sodium in mice

Abstract

• Protective effect of COS on the DSS-induced chronic experimental UC development. • Anti-inflammatory and anti-apoptotic activities of COS in chronic UC mice. • COS promoted the proliferation of crypt epithelial cells in chronic UC mice. • COS modulated gut microbiota in chronic UC mice. • Possible involvement of TLR4 signal pathway in COS-mediated protection in chronic UC. • Possible involvement of colonic Reg3g in COS-mediated protection in chronic UC. Chitooligosaccharides(COS) as potential functional food has been paid great attention because of their outstanding biological activities. Here, we found COS (250 and 500 mg/kg) protected against development of dextran sodium sulfate(DSS)- induced chronic experimental ulcerative colitis(UC) in mice. DSS-elevated serum and colonic tumor necrosis factor(TNF)-α, interleukin(IL)-1β and IL-6 levels were significantly supressed. TUNEL + apoptoic cells and Cleaved Caspase-9 expression were downregulated, Ki-67 + proliferative cells in colonic crypts and Bcl-2/Bax ratio were upregulated in COS-treated colons compared to DSS controls. COS enhanced gut microbiota diversity and restored community structure in chronic UC mice. Colonic expression of TLR4, NF-κB, STAT3 and pSTAT3 was significantly decreased, but that of regenerating islet derived 3 gamma(Reg3g) was increased by COS. Overall, COS represents a treatment alternative in chronic UC management via ameliorating inflammation, promoting mucosal repair and modulating gut microbiota. Inhibition of TLR4 signal and induction of colonic Reg3g might be involved in molecular mechanisms.