Melatonin prevents the dysbiosis of intestinal microbiota in sleep-restricted mice by improving oxidative stress and inhibiting inflammation.

BACKGROUND

Intestinal inflammation caused by sleep restriction (SR) threatens human health. However, radical cure of intestinal inflammatory conditions is considerably difficult. This study focuses on the effect of melatonin on SR-induced intestinal inflammation and microbiota imbalance in mice.

METHODS

We successfully established a water platform to induce long-term SR in mice for 28 days with or without melatonin supplementation. The SR-induced oxidative stress and inflammatory changes were evaluated in plasma and jejunum tissue samples using in vitro assays. Additionally, changes in the intestinal microbiota were explored using high-throughput sequencing of the 16S rRNA gene.

RESULTS

After 20 h of chronic sleep restriction for 28 consecutive days, plasma melatonin was significantly reduced by 48.91% (P < 0.05), while GLU, NE, and CORT were significantly increased (34.32%-90.28%, P < 0.05). The activities of antioxidant enzymes (SOD, GSH-Px, and CAT) and T-AOC in intestinal tissues of SR mice were decreased (17.02%-40.92%, P < 0.05), while the content of MDA was increased (15.12%, P = 0.0089). The levels of pro-inflammatory cytokines (IL-6 and TNF-α) ware increased (65.27%-123.26%, P < 0.05), while the levels of anti-inflammatory cytokines (IL-10 and IFN-γ) were decreased (26.53%-60.41%, P < 0.05). High-throughput pyrosequencing of 16S rRNA from jejunum samples demonstrated an overall increase in the number of OTUs (30.68%, P = 0.015). The α-diversity (Shannon, ACE and Chao1) of jejunum was increased (28.18%-48.95%, P < 0.05), and the β-diversity (PCoA and NMDS) was significantly different from that of the control group (P = 0.001). Furthermore, the prevalences of Helicobacter and Clostridium were higher, whereas that of Bacteroidetes and Lactobacillus were lower in SR mice than in controls (P < 0.05). However, melatonin supplementation reversed the SR-induced changes and improved oxidative stress, inflammatory response, and microbiota dysbiosis in the jejunum, and there was not significant difference compared with the control group (P > 0.05).

CONCLUSIONS

Melatonin prevents the dysbiosis of intestinal microbiota in SR mice by improving oxidative stress and inhibiting inflammation. Our results may provide a theoretical basis for conducting clinical research on insufficient sleep leading to intestinal health in humans and hence facilitate a better understanding of the role of melatonin.