Melatonin is known for its role in regulating the sleep–wake cycle, but it has additional roles in the body including the support of antioxidant status and a healthy inflammatory response. It also may play a role in maintaining a balanced gut microbiota. Many of these roles may help support gut health.

Melatonin is secreted from the pineal gland, where it regulates the immune system and circadian rhythm. Some melatonin is also synthesized in the intestines by enterochromaffin cells and gut microbes, where it acts locally rather than entering systemic circulation. Some of this melatonin may also come from dietary sources. Studies have found there is 400 times more melatonin in the gut than in the pineal glands and 10 to 100 times the amount found in serum, demonstrating its importance to gut function.

The melatonin in the gut supports immune function in the gut, including interacting with immune cells, promoting a healthy inflammatory response, and supporting antioxidant status. Melatonin directly scavenges reactive species and increases the activities of antioxidant enzymes. It may also regulate inflammatory pathways, including nuclear factor kappa-B (NF-κB). Melatonin receptors are also found on some immune cells, including T cells, where it promotes the differentiation of CD4+ naïve T cells into TH cells that modulate the immune response. B cells also have melatonin receptors, and melatonin has been shown to increase the response of B cells to antigens. Melatonin may also support the production of certain inflammatory cytokines to regulate an immune response.

Melatonin may support a healthy gut microbiome. It may act as an endocrine transmission signal from commensal microbes to affect the molecular clock of microbes similar to its function as regulating circadian rhythms in humans. This regulation of the microbes may also affect the rhythm of the production and circulation of their metabolites. Melatonin may also affect gut motility, as it stimulates receptors to produce smooth muscle relaxation or contraction.

Sleep deprivation and other causes of reduced melatonin levels may negatively affect gut health. One study with participants who had chronic, heavy alcohol use found a correlation between lower melatonin levels and increased intestinal permeability and markers for endotoxemia. Another study on young adults seeking psychiatric care with primarily anxiety disorders, affective disorders, or both, found a correlation between dysfunction in melatonin levels and IBS. Higher levels of melatonin after lunch were positively associated with gastrointestinal symptoms.

Supplementing with melatonin may support gut health.* In one study on mice, the mice were subjected to sleep deprivation, which led to a decrease in melatonin levels, a reduction in antioxidant defenses, an increase in inflammation, and injury to the colonic mucosa. There was also a decrease in the diversity of the gut microbiota, including a reduction in Akkermansia, Bacteroides, and Faecalibacterium, and an increase in the potentially pathogenic species of Aeromonas. After supplementation of 20 and 40 mg/kg of melatonin, there was an improvement in the mucosal injury and dysbiosis. The melatonin supplementation also supported antioxidant status and promoted a healthy inflammatory response.*

Studies have demonstrated an important role of melatonin in supporting many aspects of gastrointestinal function.* Maintaining a normal circadian rhythm and sleep schedule may help support healthy melatonin synthesis and metabolism to support gut health.* The use of supplemental melatonin for treating gastrointestinal disorders remains under investigation but it has shown promising results.

By Kendra Whitmire, MS, CNS