The Enteric Nervous System and Its Emerging Role as a Therapeutic Target

Abstract

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation, and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection, or inflammation of the ENS highlight its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI diseases including short bowel syndrome with neuronal pathophysiology and current therapies. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances and ultimately change our treatment approach.

Could Chronic Idiopatic Intestinal Pseudo-Obstruction Be Related to Viral Infections?

“…Finally, the pivotal action of the ENS in certain diseases of the gastrointestinal tract, and the identification of receptors on the enteric neuron for hormones and transmitters, suggests the rational basis for current and future targeted therapies potentially helping patients suffering from a broad range of gastrointestinal disorders [ 94 ].…”

“…Finally, the pivotal action of the ENS in certain diseases of the gastrointestinal tract, and the identification of receptors on the enteric neuron for hormones and transmitters, suggests the rational basis for current and future targeted therapies potentially helping patients suffering from a broad range of gastrointestinal disorders [94]. Some reports showed that immunomodulatory/immunosuppressive therapies were effective in CIIPO with an inflammatory neuropathy, if antineuronal antibodies are detected (ANNA-1 or anti-Hu), or in autoimmune-induced CIIPO [19,95,96].…”

The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease

“…Finally, probiotics, diet, and nutritional supplements, as well as fecal microbiota transplantation, have been proposed to slow down the clinical progression of Parkinson’s disease [ 85 ]. In this respect, the ENS represents a potential therapeutic target for common GI diseases [ 86 ].…”

Peripheral Nervous System Involvement in Non-Primary Pediatric Cancer: From Neurotoxicity to Possible Etiologies

“…Changes in the density and morphology of enteric neurons, so called enteric neuropathy, have been implicated in a wide range of GI disorders including achalasia, Hirschsprung’s disease, slow-transit constipation and chronic intestinal pseudo-obstruction [ 181 , 182 ]. Enteric neuropathies are emerging as key players in chemotherapy-induced GI dysfunction [ 183 ].…”