Chitosan Oligosaccharides Alleviate Colitis by Regulating Intestinal Microbiota and PPARγ/SIRT1-Mediated NF-κB Pathway

• Published in: Marine drugs Vol. 20; no. 2; p. 96
• Main Authors: Guo, Congcong, Zhang, Yue, Ling, Tao, Zhao, Chongjie, Li, Yanru, Geng, Meng, Gai, Sailun, Qi, Wei, Luo, Xuegang, Chen, Liehuan, Zhang, Tongcun, Wang, Nan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-01-2022; MDPI
• Subjects: Abundance; Acetylation; Animals; Cells; Chitosan; Chitosan - pharmacology; chitosan oligosaccharides; Colitis; Colitis - drug therapy; Colitis - microbiology; Cytokines; Dextran; Dextrans; Disease Models, Animal; Gastrointestinal Microbiome - drug effects; Inflammation; Inflammatory bowel disease; Interleukin 6; intestinal microbiota; Intestinal microflora; Intestine; Lipopolysaccharides; Lysine; Male; Mice; Mice, Inbred C57BL; Microbiota; Mucin; NF-kappa B - metabolism; NF-κB; NF-κB protein; Nitric oxide; Oligosaccharides; Oligosaccharides - pharmacology; Peroxisome proliferator-activated receptors; Phosphorylation; PPAR gamma - metabolism; PPARγ; Propionic acid; Proteins; RAW 264.7 Cells; Signal transduction; Signal Transduction - drug effects; siRNA; SIRT1; SIRT1 protein; Sirtuin 1 - metabolism; Sodium; Sodium sulfate; Synaptotagmin; Tumor necrosis factor-TNF; ulcerative colitis; chitosan oligosaccharides; NF-κB; intestinal microbiota; ulcerative colitis; SIRT1; PPARγ
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20020096

Chitosan oligosaccharides (COS) have been shown to have potential protective effects against colitis, but the mechanism underlying this effect has not been fully elucidated. In this study, COS were found to significantly attenuate dextran sodium sulfate-induced colitis in mice by decreasing disease activity index scores, downregulating pro-inflammatory cytokines, and upregulating Mucin-2 levels. COS also significantly inhibited the levels of nitric oxide (NO) and IL-6 in lipopolysaccharide-stimulated RAW 264.7 cells. Importantly, COS inhibited the activation of the NF-κB signaling pathway via activating PPARγ and SIRT1, thus reducing the production of NO and IL-6. The antagonist of PPARγ could abolish the anti-inflammatory effects of COS in LPS-treated cells. COS also activated SIRT1 to reduce the acetylation of p65 protein at lysine 310, which was reversed by silencing SIRT1 by siRNA. Moreover, COS treatment increased the diversity of intestinal microbiota and partly restored the
/
ratio. COS administration could optimize intestinal microbiota composition by increasing the abundance of
,
and
while decreasing the abundance of
. Furthermore, COS could also increase the levels of propionate and butyrate. Overall, COS can improve colitis by regulating intestinal microbiota and the PPARγ/SIRT1-mediated NF-κB pathway.