Vagus nerve-mediated intestinal immune regulation: therapeutic implications of inflammatory bowel diseases

Abstract

The pathophysiology of inflammatory bowel disease (IBD) involves immunological, genetic and environmental factors. Through its ability to sense environmental stimuli, the autonomic nervous system plays a key role in the development and persistence of IBD. The vagus nerve (VN), which contains sensory and motor neurons, travels throughout the body to innervate the gut and other visceral organs in the thoracic and abdominopelvic cavities. Recent studies show that the VN has anti-inflammatory effects via the release of acetylcholine, in what is known as the cholinergic anti-inflammatory pathway (CAIP). In the gut immune system, the CAIP is proposed to be activated directly by signals from the gut and indirectly by signals from the liver, which receives gut-derived bioactive substances via the portal vein and senses the status of the gut. The gut–brain axis and liver–brain–gut reflex arc regulate a wide variety of peripheral immune cells to maintain homeostasis in the gut. Therefore, targeting the neural reflex by methods such as VN stimulation is now under investigation for suppressing intestinal inflammation associated with IBD. In this review, we describe the role of the VN in the regulation of intestinal immunity, and we discuss novel therapeutic approaches for IBD that target neuroimmune interactions.

Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

“…As the most important parasympathetic nerve, vagus nerve was widely distributed in the digestive system. Vagus nerve-mediated cholinergic anti-inflammatory pathway was an important pathway for central nervous system to maintain intestinal homeostasis [ 28 ]. Therefore, we further explored whether altered intestinal homeostasis after Aβ 1–42 administration was achieved through inhibition of cholinergic anti-inflammatory pathways.…”

Bioelectronic medicine for restoring autonomic balance in autoimmune diseases

“…VNS and SNS) activate the enteric neurons, which in turn activate the anti-inflammatory α7 nAChR-expressing macrophages resident in the intestinal mucosa. [105][106][107] In both the spleen and intestines, activation of the α7 nAChRexpressing macrophages inhibits the release of proinflammatory cytokines. [107,108] Interestingly, while the intestinal mucosa contains both the α7 nAChRexpressing macrophages and the α7 nAChR-expressing dendritic cells, only the former were shown to be activated by the VNS.…”

Immunological Tolerance in Liver Transplant Recipients: Putative Involvement of Neuroendocrine-Immune Interactions

“…The interactions between immunoregulatory cells and the nervous system may be key factors in understanding immunological tolerance mechanisms involved in transplantation and autoimmune diseases. Furthermore, psycho-emotional illnesses and bio-psychosocial disorders, such as maternal-fetal deprivation in the early years, play important roles in inducing the intestinal inflammatory response and in Crohn’s disease rates, suggesting a possible inflammatory modulation loop via brain-gut interactions [ 133 , 134 ]. Patients with end-stage cirrhotic liver disease and hepatitis and post-transplant patients have a high incidence of depression, a condition that may be controlled by a reduction in hepatic encephalopathy through the use of antidepressants [ 135 ].…”