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.