Nonruminant Nutrition Symposium: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract.

This research article discusses the role of the gut’s neural and endocrine systems in digestive disorders. It covers examples of enteric neuropathies in both humans and agricultural animals, the impact of certain diseases on these systems, and the potential for future treatments to target these areas for more effective management of digestive conditions.

The Gastrointestinal Tract

• The study emphasizes the critical role of the enteric nervous system (ENS) and the gastroenteropancreatic (GEP) endocrine system in the functioning of the gastrointestinal tract. ENS is the most extensive system of peripheral neurons, whereas the GEP endocrine system is the largest endocrine system in the body.
• The ENS in large mammals contains 500 million neurons, while the GEP endocrine system produces more than 30 hormones. Hence, these systems are vital for regulating digestive processes and can significantly affect health when disrupted.

Enteric Neuropathies and Digestive Disorders

• Various enteric neuropathies affect both humans and animals, including commercially significant species like horses and cattle. These may include lethal conditions such as lethal white syndrome in horses and Hirschsprung’s disease in humans.
• Common disorders such as ileus in horses lead to euthanisation due to the debilitating impact on the animals’ health and quality of life.

Examples of Enteric Neuropathies

• The article reviews different cases of enteric neuropathies affecting agricultural animals and humans, such as prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea.
• Prion proteins are located in the enteric neurons and glia and play a role in transmitting infection from the gut to the brain and vice versa.
• Postoperative ileus is a complex disorder resulting from the local inhibitory effects of sympathetic nervous system activation and opioid release, presumably from enteric neurons. It also involves intestinal inflammation.
• Conversely, lethal white syndrome in horses, Hirschsprung’s disease in humans, and similar conditions in mice and rats result from congenital distal bowel aganglionosis. Mutations of the same genes cause the condition in these species, and the only effective treatment currently is surgical removal of the aganglionic bowel.
• Similarly, infectious diarrheas involve the activation of enteric secretomotor neurons by pathogens or their toxins, leading to significant fluid loss. However, there are no developed strategies yet to target enteric neurons in treating secretory diarrheas.

Disorders of Enteroendocrine Cells

• Disorders of enteroendocrine cells, aside from GEP endocrine tumors, are less well-documented, but some evidence points to the involvement of gut endocrine cells in irritable bowel syndrome and celiac disease symptoms in certain patients.
• Continued research into these enteric neural and endocrine signaling systems could lead to improved diagnostic and treatment strategies, especially regarding digestive disorders in agricultural and companion animals.