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What is Motilin? Its Function & Role in Gut Health

Written by Joe Cohen, BS | Reviewed by Joe Cohen, BS, Nattha Wannissorn, PhD (Molecular Genetics) | Last updated:

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Motilin is a very important enzyme in the digestive system. It helps move food through the digestive tract by causing muscle contractions. Read on to learn more about this hormone, its effects on your body and associated complications.

What is Motilin?

Motilin is a hormone produced by cells in the small intestine. Motilin is named so because it stimulates movement (motility) of digestive organs. Its main function is to cause movement and emptying of the digestive tract by initiating intestinal muscle contractions [1, 2].

Blood motilin rises during fasting periods and after digesting a meal, but they disappear during food consumption. Its release is influenced by water, fat, and pressure in the digestive system (mechanically-induced release) [1, 2, 3].

Motilin secretion in the small intestine is important because this organ is responsible for digestion and nutrient absorption. Motilin release is strongly blocked during pregnancy, so pregnant women have significantly lowered motilin levels [1, 2, 3].

Motilin Function

Motilin regulates the migrating motor complex (MMC). This complex is involved in the muscle activity of the digestive system. In humans, MMC activity starts in the upper gut [2, 4].

The MMC has a few phases, where phase III is controlled by motilin and is the most important phase. This stage involves a burst of muscle contractions originating at the beginning of the small intestine (duodenum) and moves along all the way to the end. Phase III is also involved in hunger [5, 4, 2, 1].

Motilin increases the action of acetylcholine, which is what causes intestinal muscles to contract in the gut [4, 2, 1].

This process clears the small intestine of undigested food, preventing bacterial overgrowth and stimulating hunger. Additionally, it ensures leftover debris does not block nutrient absorption in the small intestine. There is a high-risk for a nutrient deficiency if there is debris in the small intestines blocking absorption [4, 2, 1].

Migrating Motor Complex (MCC) and the Vagus Nerve

The vagus nerve is a major component in the rest-and-digest system (parasympathetic nervous system). The vagus nerve controls the migrating motor complex (MMC) in the stomach. Cutting this nerve stops MMC activity in the stomach, but not in the small intestine (MMC phase III intact) [6, 4, 1].

While the vagus nerve regulates levels of digestive hormones like gastrin and other pancreatic enzymes, it does not control motilin levels. However, in an experiment where the vagus nerves of dogs got blocked, motilin levels had a higher peak during phase III of MMC [6, 4, 1].

Motilin Receptors

Motilin receptors are found in the digestive tract (stomach, colon, and small intestine). The highest concentration of human receptors for motilin is found in the narrow part of the stomach (pyloric antrum). These receptors are functionally (and possibly structurally) different than those found in other species like rabbits [7, 8].

Motilin receptors are also found in the brains of mice, which may be true for humans too [9].

Health Aspects of Motilin

Motilin levels rise and fall throughout the day cyclically. To measure your blood motilin levels, you’d have to fast for about 10 hours before the test. One study with 38 healthy individuals saw a big variation in fasting blood motilin ranges (50 – 545 pg/mL). The average was 217 pg/mL [10].

Abnormally high motilin levels may cause some negative health effects, while motilin therapy has benefits (asides from the normal functions in the body) [2].

High Motilin Associations With Disease

High Motilin Associated with Ulcers

Motilin levels were analyzed in 26 patients with ulcerative colitis (inflammation and ulcers in the digestive tract). These individuals had abnormally high motilin levels (350 – 1000 pg/mL) relative to the control and general population [11].

Increased food movements and small intestinal contractions (from high motilin) cause diarrhea and acidification of the digestive tract (bicarbonate release to balance acid is obstructed) [11].

High Motilin Associated with Diabetes

38 normal and 41 diabetic individuals were tested to evaluate their blood motilin levels. In diabetic patients, fasting blood motilin levels were significantly higher than in normal individuals. While there was overlap between healthy and diabetic individuals at about 200 – 400 pg/mL, only diabetic individuals had blood motilin levels greater than 550 pg/mL [10].

Motilin can be Potentially Beneficial

Motilin May Treat Symptoms of Diabetes

Nerve damage in diabetics is common, and if damaged in the digestive system, can lead to digestive problems including constipation (diabetic gastroparesis). 9 diabetic patients had significantly impaired ability to empty the food content from their stomach [12].

Motilin therapy (intravenously) restored stomach emptying in diabetic individuals. Motilin and similar derivatives are useful in treating such digestive issues in diabetic patients [12].

Motilin May Reduce Anxiety

A study using mice administered motilin directly into the brain and found a significant decrease in anxiety. They ensured that this effect was through motilin by using a motilin receptor blocker (which reversed the effect) [9].

Motilin Drug Interactions

Drugs that mimic the structure and action of motilin is of high interest to researchers. Drugs that increase the activity of motilin receptors, also called motilides, help reduce nausea and increase gastric emptying (in diabetics). The most important phase (III) of the migrating motor complex (MMC) is triggered by the administration of motilin and other functionally similar drugs [13].

Drugs that block motilin receptors are also a growing field of research. In theory, these types of drugs help with digestive conditions that are caused by too much food movement in the bowels (hypermotility). They have potential use in treating conditions like diarrhea and irritable bowel syndrome (IBS) [1].

Motilides (Motilin Receptor Activators)

Erythromycin

Erythromycin, an antibiotic normally used to treat infections, is also a potent activator of motilin receptors. One study (RCT) evaluated the use of erythromycin to stimulate hunger and food intake in 14 healthy volunteers. They found significant positive results, suggesting erythromycin use to stimulate hunger and food intake [14, 5].

ABT-229, an erythromycin derivative, strongly increased gastric emptying with a single dose (4 – 16 mg) in a study (DB-RCT) involving nine healthy volunteers [15].

Azithromycin

Another antibiotic, azithromycin, also activates motilin receptors similarly to erythromycin. A retrospective study compared azithromycin and erythromycin in improving gastric emptying in 120 patients with digestion problems (gastroparesis). Both drugs were equivalent in improving gastric emptying of the patients, although azithromycin has less severe side effects [16, 17].

Camicinal

Two studies (DB-RCT’s) gave varying doses of camicinal to healthy individuals (8 individuals in one study, 12 in the other) to evaluate its potential use in treating digestive problems. Camicinal helps to improve gastric emptying and may improve symptoms of heartburn (gastroesophageal reflux disease) at single doses of 125mg and 150mg [18, 19].

Altimotin

In two placebo-controlled studies, altimotin was administered into the blood (intravenously) in 10 and 48 healthy volunteers. Both studies concluded that altimotin increases gut motility and may be used to treat digestive problems.

Mitemcinal (GM-611)

392 diabetic patients with digestive problems (gastroparesis) were either given a placebo, 5 mg of mitemcinal or 10 mg of mitemcinal for three months. Patients receiving mitemcinal had significantly improved digestion (gastric emptying) compared to those who only received a placebo [20].

Motilin Receptor Blockers (Antagonists)

Experimental motilin blockers reduced bowel contractions in animals and helped treat diarrhea caused by motilin administration [21, 22, 23].

Motilin administration into the brain significantly reduces anxiety in mice. Giving mice a motilin blocker reversed the anxiety effects of motilin in the brain [9].

Motilin Genetics

Health Risks

A population-controlled study linked the motilin receptor gene, MLNR, to increased risk of cancer and gallstones. This study, which included almost 1,500 participants (439 biliary cancer, 429 gallstones, and 447 controls), concluded that the risk of gallstones and biliary (gallbladder/liver) cancers significantly increases with two versions (mutations) of this gene (MLN rs2281820 and MLNR rs9568169, respectively) [24].

Limitations/Caveats

Most research involving motilin is focused on developing motilin receptor activators or blockers. Clinical trials evaluating abnormally high or low motilin levels are very limited. Additionally, the effects of motilin in other parts of the body outside of the digestive system are still being speculated.

About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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