Low Melatonin in the Gut Can Increase Risk of Neurological Disorders


Melatonin is linked to circadian rhythm, mitochondrial function, and neuroinflammation.

A dysregulated gut microbiota may be linked to reduced melatonin production, increasing the risk of neurological disorders, according to the results of a recent study published in Biomedicine & Pharmacology. However, managing this network of biological interconnections, also called the "gut-microbiota-brain (MGB) axis,” can improve health outcomes and may reduce risk of neurologic disease progression or risk.

Drawind of human brain on chalkboard with inscription melatonin | Image Credit: iushakovsky - stock.adobe.com

Image Credit: iushakovsky - stock.adobe.com

“The potential connection between melatonin and the MGB axis suggests that the enteric microbiota may play a significant role in brain-related diseases through melatonin modulation in the gut,” authors wrote in the study.

Melatonin is a hormone molecule that manages circadian rhythm and has antioxidant and immunomodulatory effects. Largely synthesized in the pineal gland, it can also be synthesized in other organs, namely the gut, where gut microbiota biosynthesizes melatonin from the amino acid tryptophan.

Accordingly, gut dysbiosis can impact melatonin production, and people with low melatonin production have higher risk of suffering from disease. Low melatonin levels have been especially linked to neurological diseases, with previous studies connecting low levels with risk of Alzheimer disease, Parkinson disease, and multiple sclerosis.

Investigators conducted this review to better understand melatonin’s function, the impact of the gut microbiota on melatonin production, and possible therapeutic effects for neurological disease.

Melatonin reduces the formation of reactive oxygen species (ROS), linked to neurological disorders. It also reduces risk of autoimmune, inflammatory, and mitochondrial disorders, and promotes the production of antioxidant glutathione, which prevents cell toxicity.

In addition, melatonin is linked to better mitochondrial function by reducing oxidative stress, preserving membrane potential, upregulating durable mitochondrial proteins, improves ATP synthesis, and promotes homeostasis. Mitochondrial dysfunction is associated with the pathology of neurological diseases.

Key Takeaways

  1. A dysregulated gut microbiome (dysbiosis) may decrease melatonin production, impacting brain health.
  2. Low melatonin has been linked to Alzheimer's, Parkinson's, and multiple sclerosis.
  3. Melatonin supplementation may be therapeutic due to its anti-inflammatory and neuroprotective properties.

Perhaps most well-known is the role of melatonin in regulating circadian rhythm, regulates this natural process via environmental cues, like light and temperature. Disruptions in the circadian rhythm can boost the likelihood of developing neurodegenerative disorders, often starting years before symptom onset, which can then impact the sleep-wake cycle further and promote disease progression.

Thus, the gut microbiota and melatonin production “coordinate and intensify one another,” authors wrote.

In the review, investigators also identified studies which show how gut dysbiosis increases neuroinflammation, which can promote Alzheimer pathology. Gut dysbiosis and a reduction in melatonin production both served to reduce mitochondrial function, which increases disease risk.

Further, gut dysbiosis can promote intestinal permeability, promoting the circulation of toxic and inflammatory markers into the bloodstream and increasing systemic inflammation, a known risk factor in Alzheimer disease pathology.

Melatonin can be therapeutic in the treatment of neurological diseases, as it reduces many of the inflammatory markers associated with disease pathology— including oxidative stress, neuroinflammation, apoptosis, and mitochondrial dysfunction, and poor neurotransmission— while promoting the growth of beneficial classes of gut bacteria and reducing inflammation-promoting strains, so supplementation could be therapeutic.

Improving gut health may also improve the production of melatonin and decrease risk of neurological disease, as the gut microbiota regulates melatonin production, and reducing inflammation, increasing blood melatonin, and managing mitochondrial function are other ways to reduce risk or disease progression.

Neurological disorders may have different effects on pineal-derived melatonin versus gut-derived melatonin, so more research should be conducted. Investigators can also evaluate the role of probiotics and prebiotics on gut health, melatonin production, and neurological disease outcomes.


Ahmadi S, Taghizadieh M, Mehdizadehfar E, et al. Gut microbiota in neurological diseases: Melatonin plays an important regulatory role. Biomed & Pharma (174) 116487, 2024. DOI:10.1016/j.biopha.2024.116487

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