Ameliorative effect of an acidic polysaccharide from Phellinus linteus on ulcerative colitis in a DSS-induced mouse model.

Phellinus linteus, a rare medicinal fungus, displays strong antitumor and anti-inflammatory activities because of its active metabolites, particularly polysaccharides. We investigated effects of P. linteus acidic polysaccharide (PLAP) on amelioration of dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in a mouse model, and associated mechanisms. PLAP treatment alleviated major UC symptoms (weight loss, reduced food intake, increased disease activity index), and ameliorated histopathological colon tissue damage, reduced levels of pro-inflammatory factors (TNF-α, IL-6, IL-1ß), enhanced anti-inflammatory factor IL-10 level, reduced levels of oxidative stress-related enzymes iNOS and MPO, and enhanced expression of tight junction proteins (ZO-1, occludin, claudin-1). qPCR analysis revealed that PLAP downregulated phosphorylation levels of p65 and p38 and transcriptional level of TLR-4. High-throughput sequencing showed that PLAP restored gut microbiota diversity and species abundances in the UC model, and gas chromatographic analysis showed that it increased levels of beneficial short-chain fatty acids. Our findings indicate that PLAP has strong potential for development as an anti-UC agent based on its reduction of inflammation and oxidative stress levels, modulation of gut microbiota composition, and promotion of normal intestinal barrier function.

Clostridium butyricum and Chitooligosaccharides in Synbiotic Combination Ameliorate Symptoms in a DSS-Induced Ulcerative Colitis Mouse Model by Modulating Gut Microbiota and Enhancing Intestinal Barrier Function.

Effects of Clostridium butyricum and chitooligosaccharides (COS), singly and in synbiotic combination, were evaluated in a C57BL/6 mouse model of dextran sulfate (DSS)-induced acute ulcerative colitis (UC). Treatment with C. butyricum and/or COS ameliorated UC symptoms in vivo, and the strongest effects were observed for the combination in terms of reduced mortality rates and disease activity indices, increased body weight and colon length, and improved histological features. The C. butyricum and COS combination achieved the following: (i) regulated levels of inflammation-related cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1ß [IL-1ß], IL-6, IL-10) and had a stronger anti-inflammatory effect than either component alone, based on inhibition of Toll-like receptor 4 (TLR-4)/NF-κB/MAPK signaling pathway activation; (ii) enhanced intestinal barrier function by restoring levels of tight junction proteins (occludin, claudin-1, ZO-1) and MUC2; (iii) increased abundance and diversity of beneficial bacteria (gut microbiota) and reduced levels of pathogenic bacteria; and (iv) enhanced production of short-chain fatty acids. Our findings indicate that the synbiotic C. butyricum and COS combination has strong potential as a therapeutic adjuvant for UC. IMPORTANCE Ulcerative colitis (UC), an idiopathic intestinal disease characterized by continuous remission/relapse inflammatory cycles in the colonic mucosal layer, has strong adverse effects on patients' quality of life and considerable costs for health care systems. Probiotics, prebiotics, and synbiotics are regarded as potential therapeutic agents for UC, in terms of safety and efficacy. In this study, we present detailed evaluation of effects in a DSS-induced UC mouse model of a synbiotic composed of Clostridium butyricum and COS (molecular weight [MW], 2,500 Da). We found that synergistic (synbiotic) action of the C. butyricum and COS combination is more effective than either factor alone for prevention and/or therapy of UC by regulating gut microbiota and intestinal barrier function. Our findings indicate that C. butyricum and COS in combination has strong potential for development as anti-UC therapeutic drugs or adjuvant agents in pharmaceutical, food, and livestock industries. Highlights include the following. (i) The C. butyricum and COS combination ameliorated clinical UC symptoms and improved colonic morphology. (ii) The C. butyricum and COS combination displayed strong anti-inflammatory and antioxidant effects. (iii) The C. butyricum and COS combination enhanced expression of tight junction proteins. (iv) The C. butyricum and COS combination inhibited the TRL-4/NF-κB/MAPK signaling pathway. (v) The C. butyricum and COS combination modulated gut microbiota abundance and composition.

Chitin derivatives ameliorate DSS-induced ulcerative colitis by changing gut microbiota and restoring intestinal barrier function.

Chitin derivatives (CDs), including chitosan (CS), chitooligosaccharides (COS), and glucosamine (GlcN), were administrated in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. UC symptoms such as body weight loss, reduced food intake, and increased disease activity index were relieved (except GlcNL group). CDs (except GlcNL) exerted a strong protective effect on colon length and colonic structure. Treatment with CDs (except GlcNL) increased IL-10 level, reduced levels of IL-1ß, IL-6, TNF-α, myeloperoxidase, and inducible nitric oxide synthase, and enhanced expression of tight junction proteins significantly. CDs (except GlcNL) significantly upregulated IκB-α level, and downregulated p65 and p38 phosphory lation and TLR-4 mRNA transcription level, indicating inhibition of TRL-4/NF-κB/MAPK signaling pathway activity. CD treatments increased relative abundance of gut microbiota, modulated its composition, and increased the concentrations of SCFAs. Our findings indicate that CDs exert an ameliorative effect on UC by change of gut microbiota composition and restoration of intestinal barrier function.