The enteric nervous system (ENS) is the third division of the autonomic autonomic nervous system and the largest collection of neurons outside the central nervous system (CNS). The ENS has been referred to as "the brain in the gut" or "the second brain of the human body" because of its highly integrated neural circuits controlling a vast repertoire of gut functions, including absorption/secretion, splanchnic blood vessels, some immunological aspects, intestinal epithelial barrier, and gastrointestinal (GI) motility. The latter function is the result of the ENS fine-tuning over smooth musculature, along with the contribution of other key cells, such as enteric glia (astrocyte like cells supporting and contributing to neuronal activity), interstitial cells of Cajal (the pacemaker cells of the GI tract involved in neuromuscular transmission), and enteroendocrine cells (releasing bioactive substances, which affect gut physiology). Any noxa insult perturbing the ENS complexity may determine a neuropathy with variable degree of neuro-muscular dysfunction. In this review, we aim to cover the most recent update on genetic mechanisms leading to enteric neuropathies ranging from Hirschsprung's disease (characterized by lack of any enteric neurons in the gut wall) up to more generalized form of dysmotility such as chronic intestinal pseudo-obstruction (CIPO) with a significant reduction of enteric neurons. In this line, we will discuss the role of the RAD21 mutation, which we have demonstrated in a family whose affected members exhibited severe gut dysmotility. Other genes contributing to gut motility abnormalities will also be presented. In conclusion, the knowledge on the molecular mechanisms involved in enteric neuropathy may unveil strategies to better manage patients with neurogenic gut dysmotility and pave the way to targeted therapies.
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http://dx.doi.org/10.4081/ejh.2021.3289 | DOI Listing |
Unlabelled: Stress affects gastrointestinal (GI) function causing dysmotility, especially in patients. GI motility is regulated by the enteric nervous system (ENS), suggesting that stress alters ENS biology to cause dysmotility. While stress increases glucocorticoid levels through the hypothalamus-pituitary-adrenal axis, how glucocorticoids affect GI motility is not known.
View Article and Find Full Text PDFPediatr Surg Int
January 2025
Department of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, 1526-555 University Ave, Toronto, ON, M5G 1X8, Canada.
Purpose: Necrotizing enterocolitis (NEC) majorly affects premature infants, causing not only necrosis and inflammation but also feeding intolerance and gastrointestinal dysmotility, hinting at gut hormone secretion impairment. Particularly critical is the gestation period before 26 weeks where intestinal hormonal activity is partially developed, rendering preterm neonates highly susceptible to NEC. Emerging evidence suggests a role of gut hormones, especially glucagon-like peptides (GLP) in ileum development.
View Article and Find Full Text PDFGastrointestinal (GI) motility is regulated in a large part by the cells of the enteric nervous system (ENS), suggesting that ENS dysfunctions either associate with, or drive GI dysmotility in patients. However, except for select diseases such as Hirschsprung's Disease or Achalasia that show a significant loss of all neurons or a subset of neurons, our understanding of human ENS histopathology is extremely limited. Recent endoscopic advances allow biopsying patient's full thickness gut tissues, which makes capturing ENS tissues simpler than biopsying other neuronal tissues, such as the brain.
View Article and Find Full Text PDFJ Clin Med
November 2024
Department of Medicine, Section of Gastroenterology and Hepatology, Goedstrup Hospital, 7400 Herning, Denmark.
Chronic nausea and vomiting (N/V) disorders are common in clinical practice. Our primary aim was to compare total and segmental gastrointestinal transit times as well as gastric contraction patterns in patients with chronic N/V syndrome to those of healthy volunteers (HVs). In the patient group, our secondary aim was to explore how symptoms and motility patterns were affected by a serotonin HT receptor agonist (Prucalopride).
View Article and Find Full Text PDFInt J Mol Sci
December 2024
AgResearch, Palmerston North 4410, New Zealand.
Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile.
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