The enteric nervous system in gastrointestinal disease etiology

Abstract

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.

Influence of Tilia tomentosa Moench Extract on Mouse Small Intestine Neuromuscular Contractility

“…The combination of contraction and relaxation determines gut motility [24,25]. In presence of FGDIs, gut function is altered, and patients report a variety of symptoms, including motility disturbance, visceral hypersensitivity, altered mucosal and immune function, as well as changes in the gut microbiota [26][27][28]. The pathophysiology of FGIDs is still not fully understood, and various complex mechanisms appear to be implicated, mostly determining dysmotility [29,30].…”

Gut Microbiota and Neuroplasticity

“…Recently, it has been shown that that the enteric neuron-specific deletion of aryl hydrocarbon receptor (Ahr), a microbiotadependent gene, negatively affects intestinal motility, pointing to the role of Ahr as a potential biosensor in ENS neurons [31]. From a phylogenetic perspective, it has been suggested that the ENS has evolved to orchestrate the responses from gut microbes and relay them to influence gut motility [32]. ENS is responsible for the regulation of gastro-intestinal processes and is connected to the CNS through the vagus nerve [23,24].…”

“…From a phylogenetic perspective, it has been suggested that the ENS has evolved to orchestrate the responses from gut microbes and relay them to influence gut motility [32]. Whereas earlier studies focused on the relationship between the microbiota and the ENS, the existence of an intense cross-talk between the microbes in the gut and the whole nervous system has emerged over time, stimulating a new and very active area of research that is producing a growing body of experimental data from animal studies focused on the relation between the gut microbiota and the brain [33,34], suggesting that the gut microbiota is also a key mediator of gut-brain axis signaling in non-pathological conditions.…”

A rapid F0 CRISPR screen in zebrafish to identify regulators of neuronal development in the enteric nervous system

“…A large proportion of the general population in Western countries suffer from unsolved gastrointestinal (GI) symptoms drastically affecting quality of life. Diseases such as Hirschsprung disease, autism spectrum disorder, and inflammatory gut diseases affect the bowel, present with debilitating GI symptoms, and are associated with enteric nervous system (ENS) dysfunction 1,2 . The ENS innervates the GI tract and controls all essential gut functions, such as motility and nutrient uptake 3,4 .…”

“…Because few genes that regulate ENS neurogenesis have thus far been identified 3,4 , the genetic basis of many ENS disorders and gut diseases with an ENS component are not known. A recent surge in transcriptomic data has generated a wealth of novel, but functionally untested candidate genetic regulators of ENS neurogenesis 2,4,5 .…”