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Inflammatory bowel disease (IBD) is a result of a complex interplay, making development of a specific treatment a challenging task. Corticosterone was considered a risk factor of stress relative enteritis. Our previous studies found that melatonin exerts an improvement effect in sleep deprivation (SD)\u2010 induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone\u2010mediated SD\u2010induced colitis. <jats:italic>Methods<\/jats:italic>. A 72\u2010hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin\u2010mediated gut microbiota improving SD\u2010induced colitis. Further, corticosterone\u2010treated mice were assessed to the effect of melatonin on corticosterone\u2010mediated gut microbiota dysbiosis\u2010induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin. <jats:italic>Results<\/jats:italic>. SD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone\u2010supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD\u2010mice to normal mice could restore the SD\u2010like colitis, but no change in the corticosterone level, which suggested that corticosterone\u2010mediated intestinal microbiota imbalance plays a central role in SD\u2010induced colitis. Further, we demonstrated melatonin\u2010mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3\/AP\u20101\/NF\u2010<jats:italic>\u03ba<\/jats:italic>B pathway\u2010induced inflammatory response in vivo and in vitro. <jats:italic>Conclusions<\/jats:italic>. We revealed that excessive corticosterone is a core risk factor for SD\u2010induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone\u2010mediated gut microbiota inducing colitis.<\/jats:p>","DOI":"10.1155\/2021\/9981480","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T22:50:19Z","timestamp":1624488619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Melatonin Ameliorates Corticosterone\u2010Mediated Oxidative Stress\u2010Induced Colitis in Sleep\u2010Deprived Mice Involving Gut 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