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Background:  Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether  trans -Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction.   Methods:  ICR male mice were exposed to the CACS for 3 weeks.  trans -Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the treatment effects of  trans -Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis.   Results:  Administration with  trans -Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of  trans -Resveratrol in treatment of IBS-like disorder. Furthermore,  trans -Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that  trans -Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with  trans -Resveratrol.   Conclusions:  The dual effects of  trans -Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon.

trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis