Protective Effect of Uric Acid on Rat Model of Irritable Bowel Syndrome Requires Brain-Gut Communication Through...

Uric acid (UA) is an endogenous antioxidant that protects against neuroinflammatory diseases. Although irritable bowel syndrome (IBS) is considered a disorder of gut-brain interaction, the role of UA in IBS remains unclear.

An experimental rat model of IBS was induced using laser-induced shock waves (LISW) applied to the head. Hyperuricemia (HUA) was induced by intraperitoneal administration of inosine monophosphate and potassium oxonate. Visceral hypersensitivity was assessed by colorectal distension. Ileal mucosal permeability was measured using the Evans blue method. CRFR1 mRNA expression in the rectum, IL-10 and TGF-β1 expression in the ileum, and IL-1α, IL-1β, and TNF expression in the medial prefrontal cortex (mPFC) and paraventricular nucleus (PVN) were quantified by qRT-PCR. Vagal involvement was assessed using subdiaphragmatic vagotomy or atropine treatment.

LISW increased visceral hypersensitivity, ileal mucosal permeability, and rectal CRFR1 expression and reduced IL-10 expression in the ileum. HUA significantly ameliorated these changes. HUA was also associated with reduced IL-1β expression in the mPFC and reduced IL-1α and IL-1β expression in the PVN in LISW-treated animals. Importantly, the ameliorative effects of HUA on visceral hypersensitivity were abolished by vagotomy or atropine treatment.

Hyperuricemia ameliorated LISW-induced visceral hypersensitivity, improved ileal mucosal permeability, restored IL-10 expression in the ileal mucosa, and reduced proinflammatory cytokine expression in the brain. The loss of HUA-induced suppression of visceral hypersensitivity after vagotomy or atropine treatment suggests the possible involvement of vagal and cholinergic brain-gut communication.