Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats.

Brain oxytocin plays a role in gastrointestinal functions. Among them, oxytocin acts centrally to modulate gastrointestinal motility and visceral sensation. Intestinal barrier function, one of important gut functions, is also regulated by the central nervous system. Little is, however, known about a role of central oxytocin in the regulation of intestinal barrier function. The present study was performed to clarify whether brain oxytocin is also involved in regulation of intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of oxytocin dose-dependently abolished increased colonic permeability in response to lipopolysaccharide while intraperitoneal injection of oxytocin at the same dose failed to block it. Either atropine or surgical vagotomy blocked the central oxytocin-induced improvement of colonic hyperpermeability. Cannabinoid 1 receptor antagonist but not adenosine or opioid receptor antagonist prevented the central oxytocin-induced blockade of colonic hyperpermeability. In addition, intracisternal injection of oxytocin receptor antagonist blocked the ghrelin- or orexin-induced improvement of intestinal barrier function. These results suggest that oxytocin acts centrally in the brain to reduce colonic hyperpermeability. The vagal cholinergic pathway or cannabinoid 1 receptor signaling plays a vital role in the process. The oxytocin-induced improvement of colonic hyperpermeability mediates the central ghrelin- or orexin-induced improvement of intestinal barrier function. We would therefore suggest that activation of central oxytocin signaling may be useful for leaky gut-related diseases such as irritable bowel syndrome and autism.