Melatonin Ameliorates Corticosterone-Mediated Oxidative Stress-Induced Colitis in Sleep-Deprived Mice Involving Gut Microbiota

• Published in: Oxidative medicine and cellular longevity 2021, Vol.2021 (1), p.9981480-9981480
• Main Authors: Gao, Ting, Wang, Zixu, Cao, Jing, Dong, Yulan, Chen, Yaoxing
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Colitis - chemically induced; Colon; Corticosterone - adverse effects; Disease Models, Animal; Experiments; Feces; Gastrointestinal Microbiome - drug effects; Inflammatory bowel disease; Laboratory animals; Male; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Metabolism; Mice; Microbiota; Oxidative Stress; Sleep Deprivation - drug therapy; Transplants & implants
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2021/9981480

Background. 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)- induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone-mediated SD-induced colitis. Methods. A 72-hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin-mediated gut microbiota improving SD-induced colitis. Further, corticosterone-treated mice were assessed to the effect of melatonin on corticosterone-mediated gut microbiota dysbiosis-induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin. Results. SD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone-supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD-mice to normal mice could restore the SD-like colitis, but no change in the corticosterone level, which suggested that corticosterone-mediated intestinal microbiota imbalance plays a central role in SD-induced colitis. Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-κB pathway-induced inflammatory response in vivo and in vitro. Conclusions. We revealed that excessive corticosterone is a core risk factor for SD-induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone-mediated gut microbiota inducing colitis.