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The Microbiota-Dependent Worsening Effects of Melatonin on Gut Inflammation.

May 2023

da Silva JL, Barbosa LV, Pinzan CF, et al. The Microbiota-Dependent Worsening Effects of Melatonin on Gut Inflammation. Microorganisms. 2023;11(2):460. Published 2023 Feb 11. doi:10.3390/microorganisms11020460


One of the many functions of melatonin is its immune regulatory and anti-inflammatory effects. As a result, researchers sought to explore the use of melatonin in mice with colitis, dysbiosis, bacteria translocation and exacerbated immune response to understand its potential as a therapy for inflammatory bowel diseases (IBD), as there is a lack of consensus and limited studies for the use of melatonin with IBD.


Our comments/takeaway from the article

At present, there is mixed evidence for the use of melatonin as a potential therapy for IBD with 50 publications in Pubmed using the search terms “inflammatory bowel disease” and “melatonin” (as of May 11, 2023). Of these publications, there is limited clinical data to suggest that melatonin supplementation may be therapeutic for those with IBD. This is an animal (mouse) study that needs to be viewed within the larger context of existing research, concepts, and application of melatonin in IBD, which encompasses both ulcerative colitis and Crohn’s disease.  


Some important clinical concepts when it comes to recommending melatonin in clinical practice, particularly in IBD:

1. Personalization: Diseases are complex with multiple root causes. Every individual has unique nutritional needs. Having a qualified healthcare practitioner to provide personalized recommendations based on the whole person is always recommended. Within the context of IBD specifically, the status of inflammation (acute vs. chronic), dietary intake, lifestyle choices, stress level, and the quality and quantity of gut microbiota would need to be considered, to name a few.

2. The unique role of the gut: The gut mucosa makes 400 times greater levels of melatonin than the pineal gland; therefore, melatonin would seem to play a significant role in gut health. There are studies using melatonin supplementation for GERD and IBS specifically. It’s also thought that melatonin supplementation can modify the gut microbiome. The quality, type, and format of the melatonin supplement, time of day administered, interaction with dietary components, and even the quality of a person’s sleep may have contributory effects to both the action of melatonin and even the disease itself.



Article summary

This study included wild-type C57BL/6 mice to investigate the influence of exogenous melatonin in the acute phase of colitis induction, the influence of melatonin for the recovery of intestinal inflammation, and the role of the gut microbiota in the melatonin effects on intestinal inflammation. 


  • Colitis was induced by a single administration of dextran sulfate sodium (DSS). 

  • Five antibiotics were given to deplete the intestinal microbiota.

  • Melatonin was administered at 10 mg/kg at 8 am for 4 days (days 3-6 of the experiment).

  • The study lasted 7-13 days after DSS administration.


Negatively, the melatonin-treated group was shown to have:

  • Worsened DSS-induced intestinal inflammation

  • Increased weight loss

  • Higher clinical disease scores

  • Increased circulating leukocytes, mononuclear cells, and neutrophils

  • Increased Actinobacteria (commonly increased in those with Crohn’s disease)

  • Reduced Bacteroidetes (commonly reduced in those with Crohn’s disease)


Positively, in the group that was given antibiotics before DSS, a faster weight recovery and improvement in clinical disease scores were observed. The authors suggest that melatonin had a more positive impact on the disease state when the gut microbiota was first eliminated by antibiotic therapy. Therefore, it might seem that there could be an interaction between exogenous melatonin and gut microorganisms that would impact its action in IBD.


The authors conclude:

In conclusion, despite the fact that MLT could play a protective role in specific conditions of inflammation, we still should be cautious regarding its wide use to treat IBD, since hormone supplementation may exacerbate the inflammatory responses, depending on the hosts and on the gut microbiota harbored by them.”


Limitations noted by Author(s)

  • Mice bred and housed in different facilities can have different microbiota, impacting the results found in this study compared to other findings.

  • Melatonin was only administered after the establishment of colitis.


Other limitations noted in this review:

  • The type of melatonin used was not specified.



Article review completed by Kim Ross, DCN

Content reviewed by Deanna Minich, PhD

May 10, 2023

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