TY - JOUR
T1 - The enteric nervous system in gastrointestinal disease etiology
AU - Holland, Amy Marie
AU - Bon-Frauches, Ana Carina
AU - Keszthelyi, Daniel
AU - Melotte, Veerle
AU - Boesmans, Werend
N1 - Funding Information:
This work is supported by grants from the Research Foundation Flanders (FWO: G036320N) and the Dutch Research Council (NWO VIDI: 016.196.367).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/5
Y1 - 2021/5
N2 - A highly conserved but convoluted network of neurons and glial cells, the enteric nervous system (ENS), is positioned along the wall of the gut to coordinate digestive processes and gastrointestinal homeostasis. Because ENS components are in charge of the autonomous regulation of gut function, it is inevitable that their dysfunction is central to the pathophysiology and symptom generation of gastrointestinal disease. While for neurodevelopmental disorders such as Hirschsprung, ENS pathogenesis appears to be clear-cut, the role for impaired ENS activity in the etiology of other gastrointestinal disorders is less established and is often deemed secondary to other insults like intestinal inflammation. However, mounting experimental evidence in recent years indicates that gastrointestinal homeostasis hinges on multifaceted connections between the ENS, and other cellular networks such as the intestinal epithelium, the immune system, and the intestinal microbiome. Derangement of these interactions could underlie gastrointestinal disease onset and elicit variable degrees of abnormal gut function, pinpointing, perhaps unexpectedly, the ENS as a diligent participant in idiopathic but also in inflammatory and cancerous diseases of the gut. In this review, we discuss the latest evidence on the role of the ENS in the pathogenesis of enteric neuropathies, disorders of gut-brain interaction, inflammatory bowel diseases, and colorectal cancer.
AB - A highly conserved but convoluted network of neurons and glial cells, the enteric nervous system (ENS), is positioned along the wall of the gut to coordinate digestive processes and gastrointestinal homeostasis. Because ENS components are in charge of the autonomous regulation of gut function, it is inevitable that their dysfunction is central to the pathophysiology and symptom generation of gastrointestinal disease. While for neurodevelopmental disorders such as Hirschsprung, ENS pathogenesis appears to be clear-cut, the role for impaired ENS activity in the etiology of other gastrointestinal disorders is less established and is often deemed secondary to other insults like intestinal inflammation. However, mounting experimental evidence in recent years indicates that gastrointestinal homeostasis hinges on multifaceted connections between the ENS, and other cellular networks such as the intestinal epithelium, the immune system, and the intestinal microbiome. Derangement of these interactions could underlie gastrointestinal disease onset and elicit variable degrees of abnormal gut function, pinpointing, perhaps unexpectedly, the ENS as a diligent participant in idiopathic but also in inflammatory and cancerous diseases of the gut. In this review, we discuss the latest evidence on the role of the ENS in the pathogenesis of enteric neuropathies, disorders of gut-brain interaction, inflammatory bowel diseases, and colorectal cancer.
KW - Neural crest
KW - Irritable bowel syndrome
KW - Inflammatory bowel disease
KW - Hirschsprung disease
KW - Microbiota
U2 - 10.1007/s00018-021-03812-y
DO - 10.1007/s00018-021-03812-y
M3 - (Systematic) Review article
C2 - 33770200
SN - 1420-682X
VL - 78
SP - 4713
EP - 4733
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 10
ER -