Chitooligosaccharides Improves Severe Acute Pancreatitis by Reducing Intestinal Mucosal Injury and Regulating Intestinal Microbiota.

Abstract

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with persistent organ dysfunction (> 48 h) and a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Chitooligosaccharide (COS), a naturally occurring alkaline oligosaccharide, demonstrates robust anti-inflammatory, antioxidant, and regulating intestinal microbiota properties. However, the specific protective impact of COS on SAP remains to be fully elucidated. Maintaining intestinal microecological balance provides an effective method for modulating systemic infection in SAP. This study examined the effects of COS on the intestinal mucosal barrier and intestinal microbiota with SAP, and the possible mechanisms by which COS produces anti-inflammatory and antioxidant functions. The SAP model was established by injecting sodium taurocholate into the pancreaticobiliary ducts of Sprague-Dawley rats. Serum pancreatitis biomarkers, inflammatory factors, oxidative stress markers in intestinal tissue, and plasma intestinal permeability factors were measured to evaluate inflammation and intestinal injury. Western blot analysis was used to detect E-cadherin and Zonula occludens-1 (ZO-1) in intestinal tissue to assess intestinal integrity. The intestinal microbiota composition in feces was characterised through 16S rRNA sequencing. COS treatment (2.5-5 mg/mL) significantly decreased serum pancreatitis biomarkers and inflammatory factors, improved pancreatic and intestinal pathology, reduced inflammatory factors in intestinal tissues and intestinal permeability factors in plasma, increased antioxidant factors, and upregulated the protein expression of E-cadherin and ZO-1 in intestinal tissues compared to those in the normal saline treatment group. COS affected the diversity and richness of the intestinal microbiota. Oral gavage of 2.5-5 mg/mL COS improved the intestinal microflora balance and recovered intestinal barrier injury in SAP rats. Additionally, an in vitro cell model of intestinal inflammation was prepared by incubating NCM460 cells with 200 μg/mL lipopolysaccharide (LPS) for 48 h. Inflammatory factors, oxidative stress markers, and expression of p-P65-P65 were measured to explore possible mechanisms of the anti-inflammatory and antioxidant properties of COS. COS ameliorated SAP severity in our rat model by restoring intestinal barrier function and microbiota balance, suggesting potential as a therapeutic agent for SAP, pending further clinical evaluation.