NONRUMINANT NUTRITION SYMPOSIUM: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract1,2

Abstract

The functioning of the gastrointestinal tract is under the control of the most extensive system of peripheral neurons in the body, the enteric nervous system, and the largest endocrine system of the body, the GEP endocrine system. The enteric nervous system in large mammals contains 500 million neurons, and the GEP endocrine system produces more than 30 hormones. Numerous enteric neuropathies affecting both humans and animals have been described and digestive disorders affect commercially important species, such as horses and cattle. The most severe enteric neuropathies (e.g., lethal white syndrome in horses or Hirschsprung's disease in humans) can be fatal. Also, horses with ileus or other digestive disorders are commonly euthanized. In this review we discuss examples of enteric neuropathies that affect agricultural animals and humans: prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea. Enteric neurons and glia are a location of prion proteins and are involved in transmission of the infection from gut to brain and brain to gut. Postoperative ileus is a complex disorder involving the local inhibitory effects of sympathetic nervous system activation and the release of opioids, presumably from enteric neurons. Intestinal inflammation, especially of the external muscle that includes enteric ganglia, also occurs in ileus. Congenital distal bowel aganglionosis, responsible for lethal white syndrome in horses, Hirschsprung's disease in humans, and similar conditions in mice and rats, is a fatal condition if untreated. Mutations of the same genes can cause the condition in each of these species. The only effective current treatment is surgical removal of the aganglionic bowel. Infectious diarrheas involve activation of enteric secretomotor neurons by pathogens and the toxins they produce, which causes substantial fluid loss. Strategies to target enteric neurons in the treatment of secretory diarrheas have not been developed. Disorders of enteroendocrine cells, other than GEP endocrine tumors, are less well documented. However, evidence for the involvement of gut endocrine cells in a subset of patients with irritable bowel syndrome, and in the symptomology of celiac disease, has been demonstrated. Further investigation of the involvement of enteric neural and endocrine signaling systems in digestive disorders, especially in agricultural and companion animals, may lead to diagnostic and therapeutic advances.

The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control

“…Under these circumstances, no propulsive activity occurs in the aganglionic bowel, and the newborn child will die if this region is not removed. Similar absence of enteric neurons in the distal bowel is also lethal in other species, including horse (lethal white syndrome), rats and mice [60]. Degeneration of colonic enteric neurons in Chagas' disease, precipitated by infection with the protozoan Trypanosoma cruzi, causes colorectal propulsion to fail and megacolon to develop in the adult, similar to the problems associated with Hirschsprung's disease in the child [61].…”

NONRUMINANT NUTRITION SYMPOSIUM: Nutrient and neuroendocrine regulation of gastrointestinal function1

“…In the first talk, Furness and Poole (2012) introduced the EEC and how these cells release gut peptides or gut hormones, also called enteroendocrine hormones (EEH), into the lamina propria after sensing the gut content through their apical membrane. The third speaker, Sigalet (2012), focused on endocrine control of gut function by one of the EEH, glucagon-like peptide 2 (GLP-2).…”

“…Furness and Poole (2012) introduced the symposium by presenting 2 important players involved in regulation of gut function: the enteric nervous system (ENS) and the gastroenteropancreatic (GEP) endocrine system. The increasing need for animal-based food products is not a new challenge for animal producers because the continuously growing human population has doubled in the last 30 yr.…”

“…Following the introduction of the ENS and GEP by Furness and Poole (2012), the second speaker. Wood (2012), presented neurogastroenterological and immuno-neurophysiological concepts supporting the role of the ENS as a critical regulator of gut function.…”