Chitosan Ameliorates DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal Barrier Function and Improving Microflora.

Xinli Li,Cuili Zhang,Chunmei Guo,Jia Wang

doi:10.3390/ijms20225751

Abstract

Ulcerative colitis (UC) has been identified as one of the inflammatory diseases. Intestinal mucosal barrier function and microflora play major roles in UC. Modified-chitosan products have been consumed as effective and safe drugs to treat UC. The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms. KM (Kunming) mice received water/CS (250, 150 mg/kg) for 5 days, and then received 3% DSS for 5 days to induce UC. Subsequently, CS (250, 150 mg/kg) was administered daily for 5 days. Clinical signs, body weight, colon length, and histological changes were recorded. Alterations of intestinal microflora were analyzed by PCR-DGGE, expressions of TNF-α and tight junction proteins were detected by Western blotting. CS showed a significant effect against UC by the increased body weight and colon length, decreased DAI (disease activity index) and histological injury scores, and alleviated histopathological changes. CS reduced the expression of TNF-α, promoted the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1 to maintain the intestinal mucosal barrier function for attenuating UC in mice. Furthermore, Parabacteroides, Blautia, Lactobacillus, and Prevotella were dominant organisms in the intestinal tract. Blautia and Lactobacillus decreased with DSS treatment, but increased obviously with CS treatment. This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.

Highlights

Ulcerative colitis (UC) has been identified as one of the modern inflammatory diseases [1]
The dextran sulfate sodium (DSS)-alone treatment group had a significantly decreased body weight and increased disease activity index (DAI) score (p < 0.01) compared with control mice. Both CSH and CSL treatment groups reduced the body weight loss, and attenuated the increased DAI score (Figure 1A,B). These results indicated that CS effectively relieved DSS-induced UC symptoms
We proposed that the effects of CS on DSS-induced UC mice were related to the regulation of the colonic mucosal barrier function, where the expressions of ZO-1, occludin, and claudin-1 play important roles in maintaining the intestinal mucosal barrier function

Summary

Introduction

Ulcerative colitis (UC) has been identified as one of the modern inflammatory diseases [1] It is a chronic and nonspecific inflammatory bowel disease (IBD), which presents with abdominal pain, diarrhea and bloody mucopurulent stool [2], and associated with a high risk of colon cancer if not treated in a timely manner. ZOs (zonula occludens), occludin, and claudins are thought to be important integral membrane proteins which participate in TJ structural integrity by binding to a actin-cytoskeleton [5]. Intestinal microflora dysbiosis decreases the intestinal mucosal barrier function and increases bacterial translocation, and intestinal pathogenic bacteria damage structural barriers by changing intestinal TJ proteins [6]. The research works focusing on effective methods to regulate intestinal mucosal barrier function and balance intestinal microflora for treatment of UC are important

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Conclusion