Role of melatonin in sleep deprivation‐induced intestinal barrier dysfunction in mice

• Published in: Journal of pineal research 2019-08, Vol.67 (1), p.e12574-n/a
• Main Authors: Gao, Ting, Wang, Zixu, Dong, Yulan, Cao, Jing, Lin, Rutao, Wang, Xintong, Yu, Zhengquan, Chen, Yaoxing
• Format: Article
• Language: English
• Subjects: Animals; Colon - immunology; Colon - microbiology; Gastrointestinal Microbiome - immunology; gut microbiota dysbiosis; Intestinal Diseases - immunology; Intestinal Diseases - microbiology; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; intestinal mucosal injury; Male; melatonin; Melatonin - immunology; Mice; oxidative stress; Probiotics; sleep deprivation; Sleep Deprivation - immunology; Sleep Deprivation - microbiology
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/jpi.12574

Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. This study focuses on the effect of melatonin on intestinal mucosal injury and microbiota dysbiosis in sleep‐deprived mice. Mice subjected to SD had significantly elevated norepinephrine levels and decreased melatonin content in plasma. Consistent with the decrease in melatonin levels, we observed a decrease of antioxidant ability, down‐regulation of anti‐inflammatory cytokines and up‐regulation of pro‐inflammatory cytokines in sleep‐deprived mice, which resulted in colonic mucosal injury, including a reduced number of goblet cells, proliferating cell nuclear antigen‐positive cells, expression of MUC2 and tight junction proteins and elevated expression of ATG5, Beclin1, p‐P65 and p‐IκB. High‐throughput pyrosequencing of 16S rRNA demonstrated that the diversity and richness of the colonic microbiota were decreased in sleep‐deprived mice, especially in probiotics, including Akkermansia, Bacteroides and Faecalibacterium. However, the pathogen Aeromonas was markedly increased. By contrast, supplementation with 20 and 40 mg/kg melatonin reversed these SD‐induced changes and improved the mucosal injury and dysbiosis of the microbiota in the colon. Our results suggest that the effect of SD on intestinal barrier dysfunction might be an outcome of melatonin suppression rather than a loss of sleep per se. SD‐induced intestinal barrier dysfunction involved the suppression of melatonin production and activation of the NF‐κB pathway by oxidative stress.