{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:51:33Z","timestamp":1793479893722,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"the National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFE0112700"],"award-info":[{"award-number":["2018YFE0112700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"the National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["KLMAN202001"],"award-info":[{"award-number":["KLMAN202001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Open Project of Key Laboratory of Molecular Animal Nutrition of Ministry of Education, Zhejiang University","award":["2018YFE0112700"],"award-info":[{"award-number":["2018YFE0112700"]}]},{"name":"the Open Project of Key Laboratory of Molecular Animal Nutrition of Ministry of Education, Zhejiang University","award":["KLMAN202001"],"award-info":[{"award-number":["KLMAN202001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This study was conducted to investigate the protective effect of chitosan oligosaccharide (COS) against lipopolysaccharide (LPS)-induced intestinal injury. The results demonstrated that COS improved the mucosal morphology of the jejunum and colon in LPS-challenged mice. COS alleviated the LPS-induced down-regulation of tight junction protein expressions and reduction of goblet cells number and mucin expression. The mRNA expressions of anti-microbial peptides secreted by the intestinal cells were also up-regulated by COS. Additionally, COS decreased pro-inflammatory cytokine production and neutrophil recruitment in the jejunum and colon of LPS-treated mice. COS ameliorated intestinal oxidative stress through up-regulating the mRNA expressions of nuclear factor E2-related factor 2 and downstream antioxidant enzymes genes. Correlation analysis indicated that the beneficial effects of COS on intestinal barrier function were associated with its anti-inflammatory activities and antioxidant capacity. Our study provides evidence for the application of COS to the prevention of intestinal barrier dysfunction caused by the stress of a LPS challenge.<\/jats:p>","DOI":"10.3390\/antiox11071384","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"1384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Chitosan Oligosaccharide Attenuates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction through Suppressing the Inflammatory Response and Oxidative Stress in Mice"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-3486","authenticated-orcid":false,"given":"Wenjing","family":"Tao","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou 310058, China"},{"name":"Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Pei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjing","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0126-x","article-title":"Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/mi.2015.32","article-title":"New developments in goblet cell mucus secretion and function","volume":"8","author":"Birchenough","year":"2015","journal-title":"Mucosal. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s11894-010-0131-2","article-title":"Intestinal goblet cells and mucins in health and disease: Recent insights and progress","volume":"12","author":"Kim","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: A therapeutic target?","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.4049\/jimmunol.171.11.6164","article-title":"Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms","volume":"171","author":"Bruewer","year":"2003","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e25231","DOI":"10.4161\/tisb.25231","article-title":"Novel mechanism of cytokine-induced disruption of epithelial barriers: Janus kinase and protein kinase D-dependent downregulation of junction protein expression","volume":"1","author":"Naydenov","year":"2013","journal-title":"Tissue Barriers"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1089\/ars.2011.3892","article-title":"Epithelial barriers in intestinal inflammation","volume":"15","author":"John","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1152\/physrev.00040.2012","article-title":"Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases","volume":"94","author":"Bhattacharyya","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1021\/acs.molpharmaceut.8b00332","article-title":"Metformin protects against LPS-induced intestinal barrier dysfunction by activating AMPK pathway","volume":"15","author":"Wu","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1700814","DOI":"10.1002\/mnfr.201700814","article-title":"Flaxseed oil attenuates intestinal damage and inflammation by regulating necroptosis and TLR4\/NOD signaling pathways following lipopolysaccharide challenge in a piglet model","volume":"62","author":"Zhu","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.lfs.2018.11.048","article-title":"Rhein ameliorates lipopolysaccharide-induced intestinal barrier injury via modulation of Nrf2 and MAPKs","volume":"216","author":"Zhuang","year":"2019","journal-title":"Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3390\/antiox8120575","article-title":"Dietary stevioside supplementation alleviates lipopolysaccharide-induced intestinal mucosal damage through anti-inflammatory and antioxidant effects in broiler chickens","volume":"8","author":"Jiang","year":"2019","journal-title":"Antioxidants"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.ijbiomac.2018.08.139","article-title":"Extraction, chemical modification and characterization of chitin and chitosan","volume":"120","author":"Belaabed","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5328","DOI":"10.3390\/md12115328","article-title":"Bioproduction of chitooligosaccharides: Present and perspectives","volume":"12","author":"Jung","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.carbpol.2019.05.050","article-title":"A review on the preparation of chitosan oligosaccharides and application to human health, animal husbandry and agricultural production","volume":"220","author":"Yuan","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6655","DOI":"10.1016\/j.bmcl.2009.10.007","article-title":"Factors affecting anti-inflammatory effect of chitooligosaccharides in lipopolysaccharides-induced RAW264.7 macrophage cells","volume":"19","author":"Lee","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/aps.2011.10","article-title":"Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases","volume":"32","author":"Liu","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ijbiomac.2011.06.014","article-title":"Attenuation of pro-inflammatory mediators in LPS-stimulated BV2 microglia by chitooligosaccharides via the MAPK signaling pathway","volume":"49","author":"Pangestuti","year":"2011","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.carbpol.2019.05.036","article-title":"Chitosan oligosaccharide-mediated attenuation of LPS-induced inflammation in IPEC-J2 cells is related to the TLR4\/NF-\u03baB signaling pathway","volume":"219","author":"Shi","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.phrs.2012.03.013","article-title":"Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: Therapeutic efficacy and possible mechanisms of action","volume":"66","author":"Yousef","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.intimp.2010.10.016","article-title":"Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress","volume":"11","author":"Qiao","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1021\/acs.jafc.5b05195","article-title":"Chitosan oligosaccharide reduces intestinal inflammation that involves calcium-sensing receptor (CaSR) activation in lipopolysaccharide (LPS)-challenged piglets","volume":"64","author":"Huang","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.2527\/jas.2009-2771","article-title":"Chito-oligosaccharide reduces diarrhea incidence and attenuates the immune response of weaned pigs challenged with Escherichia coli K88","volume":"88","author":"Liu","year":"2010","journal-title":"J. Anim. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1800494","DOI":"10.1002\/mnfr.201800494","article-title":"Hydroxyproline attenuates dextran sulfate sodium-induced colitis in mice: Involvment of the NF-\u03baB signaling and oxidative stress","volume":"62","author":"Ji","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.carbpol.2018.11.002","article-title":"Dendrobium huoshanense polysaccharide regionally regulates intestinal mucosal barrier function and intestinal microbiota in mice","volume":"206","author":"Xie","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25679","DOI":"10.1038\/srep25679","article-title":"High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine","volume":"6","author":"Yi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"398","DOI":"10.2174\/092986711794839179","article-title":"Intestinal epithelial barrier dysfunction in disease and possible therapeutical interventions","volume":"18","author":"Catalioto","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9947","DOI":"10.1039\/D0FO01871F","article-title":"Low molecular weight chitosan oligosaccharides (LMW-COSs) prevent obesity-related metabolic abnormalities in association with the modification of gut microbiota in high-fat diet (HFD)-fed mice","volume":"11","author":"He","year":"2020","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"743492","DOI":"10.3389\/fnut.2021.743492","article-title":"Chitosan oligosaccharide ameliorates metabolic syndrome induced by overnutrition via altering intestinal microbiota","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.3390\/molecules26082199","article-title":"Exploring effects of chitosan oligosaccharides on the DSS-induced intestinal barrier impairment in vitro and in vivo","volume":"26","author":"Wang","year":"2021","journal-title":"Molecules"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3390\/md13021026","article-title":"Omega-3 fatty acid intervention suppresses lipopolysaccharide-induced inflammation and weight loss in mice","volume":"13","author":"Liu","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1142\/S0192415X20500287","article-title":"Muscone ameliorates LPS-induced depressive-like behaviors and inhibits neuroinflammation in prefrontal cortex of mice","volume":"48","author":"He","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.3748\/wjg.15.3916","article-title":"Soluble intercellular adhesion molecule-1, D-lactate and diamine oxidase in patients with inflammatory bowel disease","volume":"15","author":"Song","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bcp.2015.05.016","article-title":"Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in intestinal disorders","volume":"96","author":"Muanprasat","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/cdd.2017.14","article-title":"AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression","volume":"24","author":"Sun","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrmicro2538","article-title":"Mucin dynamics and enteric pathogens","volume":"9","author":"McGuckin","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1053\/j.gastro.2006.04.020","article-title":"Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection","volume":"131","author":"Velcich","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1007\/s00018-008-8646-5","article-title":"The trefoil factor family\u2014Small peptides with multiple functionalities","volume":"66","author":"Kjellev","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrm1203","article-title":"Trefoil factors: Initiators of mucosal healing","volume":"4","author":"Taupin","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.chom.2016.01.003","article-title":"Intestinal REG3 lectins protect against alcoholic steatohepatitis by reducing mucosa-associated microbiota and preventing bacterial translocation","volume":"19","author":"Wang","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1126\/science.1127119","article-title":"Symbiotic bacteria direct expression of an intestinal bactericidal lectin","volume":"313","author":"Cash","year":"2006","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1053\/j.gastro.2016.07.008","article-title":"Inflammation and the intestinal barrier: Leukocyte-epithelial cell interactions, cell junction remodeling, and mucosal repair","volume":"151","author":"Luissint","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.bbamem.2008.08.027","article-title":"Cytokine regulation of tight junctions","volume":"1788","author":"Capaldo","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41575-018-0025-6","article-title":"Gut microbiota-mediated inflammation in obesity: A link with gastrointestinal cancer","volume":"15","author":"Cani","year":"2018","journal-title":"Nat. Rev. Gas-troenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3390\/biomedicines8010008","article-title":"The gut microbiome and type 2 diabetes mellitus: Discussing a complex relationship","volume":"8","author":"Sikalidis","year":"2020","journal-title":"Biomedicines"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.carbpol.2018.02.058","article-title":"Chitosan oligosaccharides improve the disturbance in glucose metabolism and reverse the dysbiosis of gut microbiota in diabetic mice","volume":"190","author":"Zheng","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3390\/md18010069","article-title":"Chitooligosaccharides modulate glucose-lipid metabolism by suppressing SMYD3 pathways and regulating gut microflora","volume":"18","author":"Wang","year":"2020","journal-title":"Mar. Drugs"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109246","DOI":"10.1016\/j.biopha.2019.109246","article-title":"The protective effect of icariin and phosphorylated icariin against LPS-induced intestinal epithelial cells injury","volume":"118","author":"Xiong","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3390\/antiox10030468","article-title":"Lactobacillus delbrueckii protected intestinal integrity, alleviated intestinal oxidative damage, and activated toll-Like receptor-bruton\u2019s tyrosine kinase-nuclear factor erythroid 2-related factor 2 pathway in weaned piglets challenged with lipopolysaccharide","volume":"10","author":"Chen","year":"2021","journal-title":"Antioxidants"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1007\/s12602-020-09738-4","article-title":"Cell wall contents of probiotics (Lactobacillus species) protect against lipopolysaccharide (LPS)-induced murine colitis by limiting immuno-inflammation and oxidative stress","volume":"13","author":"Chorawala","year":"2021","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_54","first-page":"407","article-title":"Mechanism of the Nrf2\/Keap1\/ARE signaling system","volume":"76","author":"Tkachev","year":"2011","journal-title":"Biochemistry"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/7\/1384\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:52:35Z","timestamp":1760140355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/7\/1384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,17]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["antiox11071384"],"URL":"https:\/\/doi.org\/10.3390\/antiox11071384","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,17]]}}}