The Link Between Serotonin, Digestion, & IBS
We know that irritable bowel syndrome (IBS) is a functional gut-brain disorder, characterized by changes in motility of the gut, as well as an altered gut-brain connection. The disconnect between the gut and the brain are shown to be a cause of increased stress and anxiety in those with IBS, as well as the increase in symptoms from stress and hypersensitivity to pain in the gut. The more we learn about the gut, the gut-brain connection, and IBS, the more complex this condition appears to be. While there are many factors at play, one piece of the puzzle may be serotonin.
Serotonin, 5-hydroxytryptamine or 5-HT, is a neurotransmitter that sends messages between cells in the body. 90-95% of serotonin is actually created in the gut, with only 5-10% in the brain. In the gut, serotonin plays a key role in sensory-motor and secretory functions, as well as a role in immune cell activation and the regulation of gut inflammation. Outside of the gut, serotonin plays a role in bone remodeling, metabolic homeostasis (balance), and sleep. In the brain, it is thought to regulate mood, happiness, and anxiety.
The gut-brain connection is marked by the communication between the central nervous system (CNS) in the brain, and the enteric nervous system (ENS) in the gut along the HPA axis. The gut is termed the “second brain” because the ENS mimics the CNS, and can function independently of the brain. This means that the ENS is able to regulate the digestive process with the CNS. The ENS relies on neuropeptides and small molecules to regulate both intestinal motility and secretion, both necessary for proper digestion.
Serotonin is thought to be one of the most important signaling molecules involved in the peristaltic reflex, which is the neural mediated muscular activity that moves food through the gastrointestinal tract. A key to normal bowel function is how long free serotonin remains in the gut wall once it’s released.
Serotonin transporter (SERT) is an important transporter protein that is responsible for the reuptake of serotonin from the synaptic space. If reuptake is blocked, the cells can’t inactivate serotonin. Studies show that those with IBS have a significant decrease in SERT, which means they have an inadequate SERT mechanism that causes serotonin to stay around longer, triggering bowel changes. Could explain the changes in motility, as well as the hypersensitivity to pain seen in IBS.
Serotonin is stored in the basal granules of enterochromaffin (EC) cells, found in the wall of the gut. ECs release serotonin into the underlying connective tissue space of the gut lining, which contains nerve fibers that express serotonin receptors, including 5-HT3 receptors that are known to send signals encoding pain, nausea, and other noxious sensations to the central nervous system. The release of serotonin occurs as a result of mucosal stimulation. The release of serotonin triggers a cascade of other neurotransmitters, such as acetylcholine and Substance P, which excites peristaltic and secretory reflexes.
If the gut is exposed to a painful stimulus, including stretching or contractions, the nerves are stimulated and they send signals to the areas of the brain involved in pain response. Normally, these areas of the brain are activated and release chemicals that lower the pain. For those with IBS, the central nervous system may not respond correctly and the pain is not lowered. This may explain the issue of hypersensitivity seen in IBS, where symptoms are more painful than they would be in those without IBS.
Microbial metabolites, including bile acids and short-chain-fatty-acids, are shown to affect the production of serotonin to help regulate gut motility. This suggests that microbial modifications could be a way to improve symptoms of IBS. This also may support the role of microbiome diversity in IBS management.
There are some studies that have looked at specific bacterial strains and their relationship to serotonin activity. We need more research to fully understand this, but it is promising for the future of IBS management.
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Altered serotonin receptor and/or SERT function is also shown to be associated with mental disorders, including major depressive disorder and anxiety disorders. This further supports the gut-brain connection and may explain why there is an increased risk for mood disorders among those with IBS. Not only that, but sex-steroids, including estrogen and progesterone, may modulate the expression of serotonin transporter genes, which may explain the higher risk of IBS and anxiety disorders in women over men.
The connection between serotonin and IBS has led to the use of medications that block or stimulate serotonin receptors to treat abnormal bowel action. These medications may be effective treatments for altered motility and hypersensitivity, and should be discussed with your doctor. Outside of medication, we may be able to boost serotonin with different lifestyle habits, including adequate protein intake, exercise, sunlight exposure, massage, sleep, Vitamin D, and stress management.
Adequate intake of protein, paired with carbohydrates, to get plenty of the amino acid, tryptophan. Don’t overthink this - eat a well-balanced diet with a variety of foods and you’ll be fine! It’s also helpful to make sure you don’t have any nutritional deficiencies, so check on these with your annual check ups.
Aerobic exercise may trigger the release of tryptophan into the bloodstream to help more reach your brain for a desired effect.
Exposure to light appears to increase serotonin levels.
Massage therapy may increase serotonin and dopamine, another mood-boosting neurotransmitter.
A consistent sleep schedule may improve your sensitivity to the effects of serotonin.
Vitamin D is thought to facilitate serotonin production, so talk to your doctor about the role of supplementation in your diet. Getting outside also helps with this!
Stress may result in damage to neurons that produce serotonin and interfere with the function of serotonin.
Remember that with IBS, serotonin activity may not be as straight-forward. Too much or too little serotonin can have negative effects on the body, so it’s important to work with your doctor as you begin to make changes. Working closely with your medical providers can ensure you take the best steps for your body!
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