GUT-brain and brain-GUT axis revisited: Possible implications in IBD and food allergy

Previously we and others have demonstrated the role of non-adrenergic noncholinergic (NANC) neuropeptides and their receptors in the development of chronic inflammatory responses in the intestinal tract such as IBD and food allergy. Most studies concentrate on the effects of neurotransmitters or neuropeptides on immune cells associated with inflammation. Not much is known about the effects of immune mediators on peripheral and central nerves involved in intestinal inflammation. This neuro-immune brain-axis involvement has been studied in a colitis model in mice. Induction of colitis resulted in neuronal activation and cytokine production in the brain. In addition, increased cortisol levels were found in blood. These studies demonstrate that intestinal inflammation is associated with neuronal and immune responses in the brain. No role for the vagus was found in the peripheral and central effects observed in colitic mice. Primary efferent and afferent fibers, originated from NANCneurons in dorsal root ganglia (DRGs) in thoracic and lumbar regions, innervate the intestine and terminate in the superficial dorsal horn of the spinal cord, an important site of pain processing. Nociceptors are widely distributed on peripheral terminals of primary fibers throughout the intestine. We have studied whether antigen specific immune factors were able to induce activation of DRG neuronal cell cultures in vitro. It was demonstrated that antigen-specific immunoglobulin and immunoglobulin free light chains can affect primary sensory NANC neurons and therefore may contribute to local neurogenic inflammation and centrally-mediated sensations such as depression, fever and pain in IBD and food allergy.