# enteric nervous system | Symptoms, Causes, Tests and Treatment | OSANG > The enteric nervous system is a unique nerve network distributed throughout the gastrointestinal tract, from the esophagus to the anus. About 500 million nerve cells are… - Official page: https://osns.co.kr/en/encyclopedia/enteric-nervous-system - Organization: OSANG Neurosurgery ## Page content Autonomic Medicine ## enteric nervous system Enteric Nervous System The enteric nervous system (ENS) is a branch of the autonomic nervous system consisting of approximately 500 million nerve cells embedded in the wall of the gastrointestinal tract. It is called the 'second brain' as it can control digestive functions independently of the central nervous system. ## At a glance The enteric nervous system is a unique nerve network distributed throughout the gastrointestinal tract, from the esophagus to the anus. About 500 million nerve cells are arranged in two layers, the Auerbach plexus and the Meissner plexus, and autonomously perform peristalsis, secretion of digestive juices, and regulation of mucosal blood flow. There is two-way communication with the brain through the vagus nerve, which is called the gut-brain axis. Abnormalities of the enteric nervous system are associated with irritable bowel syndrome, functional dyspepsia, and early gastrointestinal symptoms of Parkinson's disease. - 01Definition and Overview - 02anatomy - 03function - 04gut-brain axis - 05Enteric nervous system abnormalities and related diseases - 06Inspection and Evaluation - 07life management ## Definition and Overview The enteric nervous system (ENS) is a unique nerve network embedded in the wall of the gastrointestinal tract and contains approximately 200 to 600 million nerve cells (average approximately 500 million). This is equivalent to the number of nerve cells in the spinal cord, and allows the digestive function to be autonomously controlled without direct commands from the central nervous system. Because of this independence, Gershon named the enteric nervous system the 'second brain' in 1999. The enteric nervous system is distributed throughout the gastrointestinal tract from the esophagus to the anus and uses more than 20 types of neurotransmitters. These include serotonin, acetylcholine, nitric oxide, dopamine, and substance P. The fact that approximately 95% of the body's serotonin is produced in the intestines shows the neurochemical importance of the enteric nervous system. The autonomic nervous system has traditionally been divided into the sympathetic and parasympathetic nervous systems, but the enteric nervous system is separately classified as a third division of the autonomic nervous system due to its complexity and independence. The enteric nervous system has a complete reflex circuit of sensory neurons, interneurons, and motor neurons, capable of processing sensory input and generating motor output on its own. ## anatomy The enteric nervous system is arranged into two major plexuses within the wall of the gastrointestinal tract. Each nerve plexus consists of a ganglion where nerve cell bodies are gathered and a bundle of nerve fibers that connect them. ### Auerbach's plexus The Auerbach plexus, also called the myenteric plexus, is located between the longitudinal and circular muscle layers of the gastrointestinal tract. It is continuously distributed throughout the gastrointestinal tract from the esophagus to the anus, and mainly regulates the motor function of the gastrointestinal tract. Motor neurons in the Auerbach plexus are divided into excitatory neurons and inhibitory neurons. Excitatory neurons secrete acetylcholine and substance P to contract muscles, and inhibitory neurons secrete nitric oxide and vasoactive intestinal peptide (VIP) to relax muscles. These two types of nerve cells work cooperatively to produce the contraction-relaxation pattern of peristalsis. ### Meissner plexus The Meissner plexus, also called the submucosal plexus, is located in the submucosa. It is well developed in the small and large intestines and mainly regulates the secretory function and blood flow of the mucous membrane. Sensory neurons in the Meissner plexus sense chemical components and mechanical stimulation of the intestinal lumen. Based on this information, it regulates the secretion of digestive enzymes, mucus, and electrolytes and changes mucosal blood flow. It is responsible for creating the microenvironment necessary for nutrient absorption. ### enteric glial cells In the enteric nervous system, in addition to neurons, enteric glial cells exist in numbers 4 to 7 times greater than neurons. Enteric glial cells perform similar functions to astrocytes in the central nervous system and are involved in supplying nutrients to neurons, regulating neurotransmitter metabolism, and maintaining the intestinal mucosal barrier. Recent studies have accumulated reports that dysfunction of enteric glial cells is associated with intestinal inflammation and functional gastrointestinal diseases. ## function ### Control of peristalsis The most core function of the enteric nervous system is the control of peristalsis. When food irritates the intestinal lining, sensory neurons detect this and transmit signals to motor neurons via interneurons. As the cricoid muscle on top of the food contracts and the cricoid muscle on the lower part relaxes, the contents move toward the anus, which is called the peristaltic reflex. This process is completed only by local reflex circuits within the enteric nervous system and occurs autonomously without intervention of the central nervous system. In animal experiments, it was confirmed that peristalsis was maintained normally even in intestinal segments where external nerve connections were completely blocked. In addition to peristalsis, the enteric nervous system programs various motor patterns such as segmentation and the migrating motor complex of the small intestine. ### secretion regulation The enteric nervous system, centered on the Meissner plexus, regulates the secretion of digestive juices. Secretion of gastric acid, bile, pancreatic juice, intestinal juice, mucus, etc. is precisely adjusted according to the nutrient composition and acidity of the intestinal lumen. When the glucose concentration in the intestinal lumen increases, the sensory neurons of the enteric nervous system detect this and there is a reflex that induces the secretion of incretin, a hormone that promotes insulin secretion. The enteric nervous system also regulates the secretion and absorption of water and electrolytes in the intestinal mucosa. Hyperactivation of the enteric nervous system's secretory reflex is also involved in the mechanism by which cholera toxin causes severe diarrhea. ### Regulation of mucosal blood flow Vasomotor neurons of the enteric nervous system regulate blood flow in the arterioles and arterioles of the submucosa. During the digestion process, it selectively increases blood flow in areas where nutrient absorption is active. Nitric oxide and VIP act as major vasodilating neurotransmitters and optimize the supply of oxygen and nutrients to the mucous membrane by regulating local blood flow. ### immune regulation The enteric nervous system closely interacts with gut-associated lymphoid tissue (GALT). Approximately 70% of the body's immune cells are distributed in the intestinal mucosa, and two-way communication occurs between nerve cells of the enteric nervous system and immune cells mediated by neurotransmitters. The enteric nervous system protects against pathogen invasion by regulating the permeability of the mucosal barrier and also plays a role in regulating the inflammatory response of the intestinal mucosa. ## gut-brain axis ### two-way communication path The gut-brain axis is a two-way communication system between the enteric nervous system and the central nervous system. The vagus nerve is the key pathway for this communication, and many of the sensory signals of the enteric nervous system are transmitted to the nucleus tractus solitarius of the brain stem via vagal afferent fibers. Downstream signals from the brain to the gut reach the enteric nervous system via vagal efferent fibers. In stressful situations, when the brain's hypothalamic-pituitary-adrenal (HPA) axis is activated, cortisol is secreted, which causes increased intestinal permeability, changes in intestinal motility, and changes in the composition of intestinal flora. This mechanism explains the phenomenon of stress during exam periods causing stomach pain and diarrhea, and the phenomenon of feeling sick when nervous. ### Intestinal microorganisms and enteric nervous system The gut microbiota is a key component of the gut-brain axis. Intestinal bacteria produce neuroactive substances such as short-chain fatty acids, tryptophan metabolites, and gamma-aminobutyric acid (GABA), which directly stimulate sensory neurons of the enteric nervous system. In a germ-free animal study, it was confirmed that mice without intestinal bacteria have incomplete development of the enteric nervous system and reduced gastrointestinal motility. There are also reports that administration of certain probiotics (e.g. Lactobacillus rhamnosus) changed the expression of GABA receptors in the brain via the vagal pathway and reduced anxiety behavior. This effect did not appear in animals with the vagus nerve cut, confirming that the vagus nerve is an essential communication route between intestinal bacteria and the brain. ### Serotonin and gut-brain communication Approximately 95% of serotonin in the body is synthesized in enterochromaffin cells of the intestinal mucosa. Serotonin secreted by enterochromaffin cells acts on the sensory nerve endings of the enteric nervous system, causing peristalsis, secretion, and gag reflex. At the same time, it transmits visceral sensory information such as satiety and nausea to the brain through vagus nerve afferent fibers. Abnormalities in the serotonin signaling system of the intestinal mucosa have been confirmed in patients with irritable bowel syndrome (IBS), and drugs targeting serotonin receptors (5-HT₃ receptor antagonists, 5-HT₄ receptor agonists) are used to treat IBS. ## Enteric nervous system abnormalities and related diseases ### irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disease that causes chronic abdominal pain and changes in bowel habits without organic lesions. Approximately 11% of the world's population is affected. Visceral hypersensitivity of the enteric nervous system is one of the key pathophysiological mechanisms. IBS patients complain of pain at lower doses than normal subjects during rectal balloon dilation, which reflects a lowered threshold of enteric nervous system sensory neurons. Abnormal communication of the gut-brain axis is also involved in the onset and maintenance of IBS. In IBS patients, the HPA axis response to stress is excessive, and brain imaging studies confirm changes in activity in visceral sensory processing areas. Based on this, IBS is currently being redefined as 'disorder of gut-brain interaction'. ### functional dyspepsia Functional dyspepsia is a disease in which epigastric pain, early satiety, and postprandial bloating recur without any organic cause. The global prevalence is approximately 10-30%. Abnormalities in the sensory and motor functions of the gastric enteric nervous system are involved, and the main mechanisms are reduced gastric accommodation and delayed gastric emptying. Gastric compliance is a reflex in which the proximal part of the stomach relaxes to accept food after a meal, and is handled by inhibitory motor neurons of the enteric nervous system. ### Parkinson's disease and enteric nervous system Alpha-synuclein aggregates, a pathological characteristic of Parkinson disease, are also found in the enteric nervous system. According to Braak's hypothesis, alpha-synuclein pathology may originate in the enteric nervous system and propagate ascending to the brain stem via the vagus nerve. In an epidemiological study supporting this, patients who underwent vagus nerve transection had an approximately 40% reduced risk of developing Parkinson's disease. In more than 80% of Parkinson's disease patients, constipation is observed 10 to 20 years before the onset of motor symptoms, suggesting early lesions of the enteric nervous system. In colonic mucosa biopsies, alpha-synuclein deposition has been confirmed even in patients before the onset of motor symptoms, and enteric nervous system pathology is being studied as an early diagnostic biomarker for Parkinson's disease. ### congenital megacolon Hirschsprung disease is a representative disease in which enteric nervous system neurons are congenitally lacking. During development, neural crest cells are unable to migrate to the distal part of the large intestine, so ganglia are not formed in that segment. The non-ganglionic segment cannot relax, resulting in functional intestinal obstruction, which occurs in approximately 1 in 5,000 newborns. The principle of treatment is surgical resection of the ganglionic segment. ### Diabetic gastrointestinal disorders Chronic hyperglycemia causes neurodegeneration in the enteric nervous system. Approximately 75% of diabetic patients report one or more gastrointestinal symptoms, gastroparesis being a representative example. Oxidative stress caused by high blood sugar damages enteric nervous system neurons and enteric glial cells, and loss of inhibitory motor neurons is especially noticeable. ## Inspection and Evaluation A single, standardized test that directly evaluates the enteric nervous system has not yet been established, but indirect evaluation is possible using the following methods. - Autonomic nervous function test: Comprehensively evaluates the functional status of the autonomic nervous system, including the vagus nerve, through heart rate variability (HRV) analysis, cardiorespiratory testing, and Valsalva maneuver. Decreased high-frequency (HF) components of HRV reflect decreased vagal tone, which may be associated with gut-brain axis dysfunction. - Gastrointestinal motility test: Gastric emptying scintigraphy diagnoses gastroparesis by quantitatively measuring the rate of stomach emptying. A colonic transit study evaluates colonic transit time using radiopaque markers. - Anorectal manometry: Measures pressure in the rectum and anus to evaluate bowel function. Hirschsprung's disease shows a characteristic finding of loss of the rectoanal inhibitory reflex. - Intestinal mucosa biopsy: Performed for research purposes, it can evaluate morphological changes in enteric nervous system neurons and alpha-synuclein deposition. - Quantitative electroencephalography (QEEG): An auxiliary tool to evaluate the central nervous system aspect of the gut-brain axis, it can be used to identify changes in brain function accompanying autonomic dysfunction. ## life management Lifestyle rules for maintaining the health of the enteric nervous system and optimizing the balance of the gut-brain axis are as follows. - Regular meals: Eating at regular times regularizes the rhythm of the migratory motor complexes of the enteric nervous system. Eating quickly or irregularly can cause intestinal motility disorders. - Dietary fiber intake: Consuming 25 to 30 g of dietary fiber per day is essential for maintaining intestinal motility and preserving the diversity of intestinal flora. Dietary fiber is converted into short-chain fatty acids by intestinal bacteria and supplies energy to the nerve cells of the enteric nervous system. - Consume fermented foods: Fermented foods such as kimchi, yogurt, and soybean paste contribute to the balance of intestinal flora by replenishing beneficial bacteria. Clinical studies have reported that probiotics alleviate anxiety and stress responses through the gut-brain axis. - Slow abdominal breathing: Breathing 6 times per minute (4 seconds for inhalation, 6 seconds for exhalation) activates the vagus nerve and improves bowel function. There is a study that showed a significant reduction in abdominal pain and constipation symptoms in IBS patients after 4 weeks of breathing training. - Regular aerobic exercise: 3-5 times a week, walking, swimming, or cycling for more than 30 minutes promotes intestinal motility and increases vagus nerve tone. Research has also shown that regular exercise increases the diversity of intestinal flora. - Stress management: Chronic stress increases intestinal permeability and disrupts enteric nervous system function through HPA axis hyperactivity. Meditation, yoga, and relaxation training help restore gut-brain axis function. - Sufficient sleep: Regular sleep of 7 to 8 hours is essential for restoring autonomic balance. Sleep deprivation increases intestinal permeability and changes the composition of intestinal flora. If symptoms persist or worsen, or if you have chronic digestive symptoms whose cause cannot be identified through routine gastrointestinal testing, you should seek specialist treatment, including evaluation of autonomic function. ## Frequently asked questions ### Q01What is the enteric nervous system? The enteric nervous system is its own neural network of about 500 million nerve cells nestled in the wall of the gastrointestinal tract from the esophagus to the anus. It is called the ‘second brain’ because it can independently control the digestive process without commands from the brain. If you have indigestion or bowel dysfunction, you may need evaluation of your nervous system, not just your gastrointestinal problems. ### Q02How do the enteric nervous system and the brain communicate? The enteric nervous system and the brain communicate in two directions with the vagus nerve as the core pathway. This is called the gut-brain axis, and signaling substances produced by intestinal bacteria are also delivered to the brain through this route. Therefore, because gut health can affect mood, stress response, sleep, etc., we recommend that you seek a comprehensive evaluation if you are experiencing emotional discomfort along with digestive symptoms. ### Q03What symptoms appear if there is an enteric nervous system abnormality? If there is an abnormality in the function of the enteric nervous system, various digestive symptoms may appear, such as chronic constipation, diarrhea, abdominal bloating, abdominal pain, and discomfort after eating. Irritable bowel syndrome and functional dyspepsia are representative related diseases, and when the cause of these symptoms cannot be confirmed through general tests such as endoscopy, dysfunction of the enteric nervous system may be suspected. ### Q04What is the relationship between Parkinson's disease and the enteric nervous system? The hypothesis that alpha-synuclein, the pathological agent of Parkinson's disease, is first discovered in the enteric nervous system and spreads to the brain along the vagus nerve is being actively studied. In fact, in more than 80% of Parkinson's disease patients, constipation precedes motor symptoms several years before they appear. Understanding the link between gut symptoms and neurological disease may help with early response. ### Q05Is there a way to test enteric nervous system function? Although there is no single method to directly test the enteric nervous system, autonomic function tests and heart rate variability (HRV) analysis can indirectly assess the state of the gut-brain axis. Gastrointestinal motor function tests and recto-anal pressure tests are also used to evaluate enteric nervous system function. You don’t have to worry because the test process can be done comfortably and painlessly. ### Q06What can you do in your daily life to support your enteric nervous system health? Maintaining regular meal times and consuming enough dietary fiber and fermented foods are helpful for the health of the enteric nervous system. Slow abdominal breathing activates the vagus nerve and contributes to improving intestinal function, and regular aerobic exercise also increases intestinal motility. Since chronic stress impairs the function of the enteric nervous system, it is recommended to also manage stress. ### Q07What is the relationship between intestinal bacteria and the enteric nervous system? Intestinal bacteria produce various signaling substances such as short-chain fatty acids and serotonin precursors, and these substances stimulate sensory neurons of the enteric nervous system. When the balance of intestinal flora is disrupted, the irritability of the enteric nervous system increases and abdominal pain, diarrhea, and constipation may occur. Please consult with your doctor as taking probiotics or adjusting your diet may help improve the intestinal environment. ## Related articles - Irritable Bowel Syndrome - sympathetic nervous system - Aging and autonomic nervous system - Autonomic dysfunction after stroke This article provides general medical information and does not replace an individual diagnosis or treatment plan. Please seek a medical assessment if symptoms persist. ## Important notice This Markdown alternative helps search and AI tools understand the public page accurately. It provides general health information and does not replace an individual diagnosis or treatment.