Abstract
Intestinal diseases caused by physiological stress have become
a severe public health threat worldwide. Disturbances in the
gut microbiota-host relationship have been associated with
irritable bowel disease (IBD), while melatonin (MT) has antiinflammatory
and antioxidant effects. The objective of this
study was to investigate the mechanisms by which MT-mediated
protection mitigated stress-induced intestinal microbiota
dysbiosis and inflammation. We successfully established a
murine restraint stress model with and without MT supplementation.
Mice subjected to restraint stress had significantly
elevated corticosterone (CORT) levels, decreased MT levels
in their plasma, elevated colonic ROS levels and increased bacterial
abundance, including Bacteroides and Tyzzerella, in
their colon tract, which led to elevated expression of Toll-like
receptor (TLR) 2/4, p-P65 and p-IκB. In contrast, supplementation
with 20 mg/kg MT reversed the elevation of the plasma
CORT levels, downregulated the colon ROS levels and inhibited
the changes in the intestinal microbiota induced by
restraint stress. These effects, in turn, inhibited the activities
of TLR2 and TLR4, p-P65 and p-IκB, and decreased the inflammatory
reaction induced by restraint stress. Our results
suggested that MT may mitigate “restraint stress”-induced
colonic microbiota dysbiosis and intestinal inflammation by
inhibiting the activation of the NF-κB pathway.
Citations
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