Neuroimmune interaction in the gut: from bench to bedside

Area of Science:

• Gastroenterology
• Neuroimmunology
• Surgical Pathophysiology

Background:

• The enteric nervous system regulates gastrointestinal motility via inhibitory non-adrenergic non-cholinergic (NANC) neurons, which release nitric oxide.
• Postoperative ileus, characterized by gut hypomotility, has a pathophysiology not fully explained by short-lasting neuronal activation.
• Recent research focuses on the late phase of postoperative ileus and its interaction with the immune system.

Purpose of the Study:

• To investigate the role of inhibitory NANC neurons in postoperative ileus.
• To elucidate the interaction between the immune system and gut innervation in the pathophysiology of postoperative ileus.
• To identify new therapeutic targets for postoperative ileus and other gastrointestinal inflammatory diseases.

Main Methods:

• Utilized rat and mouse models to study gastrointestinal motility and gastric emptying after abdominal surgery.
• Investigated mast cell degranulation, macrophage activation, and inflammatory cell influx in the gut wall.
• Examined the effects of vagus nerve stimulation, acetylcholine release, and pharmacological interventions (mast cell stabilizers, antibodies, nicotinic agonists).

Main Results:

• Abdominal surgery activates inhibitory NANC neurons, but this is transient.
• Bowel manipulation induces mast cell degranulation and macrophage activation, leading to inflammatory cell influx that paralyzes the gastrointestinal tract.
• Vagus nerve stimulation and acetylcholine release prevent this inflammatory infiltrate by inhibiting macrophage activation via nicotinic receptors.
• Pharmacological interventions targeting inflammatory cells shorten postoperative ileus.
• Mast cell activation and intestinal inflammation are observed in human patients post-surgery.

Conclusions:

• Innervation of the intestine communicates bidirectionally with the immune system.
• Inflammation activates inhibitory neural pathways, while vagus nerve stimulation can suppress immune responses, particularly macrophages.
• These findings identify novel therapeutic targets for postoperative ileus and potentially other gastrointestinal inflammatory conditions.