63P - The impact of disruption of melatonin secretion on the structural-functional changes of the microbiome and the role of the melatonin-microbiome axis in the initiation of carcinogenesis

Background

Melatonin (MT) regulates sleep and antioxidants while interacting with our microbiota. Advances in technology allow a deeper understanding of our microbiome and its environment. Research is now focused on plant-derived molecules, including sulforaphane (SFN), known for activating antioxidant responses through the Nrf2 pathway and inhibiting NF-κB. This knowledge paves the way for new research and potential treatment strategies, highlighting the potential of plant-derived molecules.

Methods

Our study observed decreased melatonin levels in 52 cancer patients with severe dysbiosis. This group also had reduced Lactobacillus acidophilus and saccharomyces boulardii. By culturing these microorganisms and adding melatonin, we saw an enhanced expression of the myrosinase gene (TGG1), and strong antiproliferative effects on cancer cultures. Our findings highlight melatonin's potential role in modulating microorganism behavior and managing dysbiosis in cancer patients.

Results

Our study found low melatonin (MT) levels in cancer patients, linked to decreased Lactobacillus acidophilus and saccharomyces boulardii levels. MT exposure enhanced myrosinase gene expression and showed antiproliferative effects on cancer cultures. The use of NO synthase inhibitor reduced SFN yield, yet MT counteracted this effect. This emphasizes MT's potential role in SFN synthesis regulation and cancer disease initiation. Particularly, in cancer patients, decreased SFN biosynthesis due to deficiency of these microorganisms and dysbiosis may increase oxidative stress, initiating cancerous conditions.

Conclusions

This finding has implications for understanding SFN synthesis regulation by NO and H2O2. Importantly, in cancer patients with a lack of Lactobacillus acidophilus and saccharomyces boulardii and MT deficiency, there's an increased risk of oxidative stress, creating conditions conducive to cancer. Unresolved is whether MT deficiency precedes the failure of these microorganisms and myrosinase gene inhibition, or if these conditions result from deep dysbiosis leading to MT deficiency.

Editorial acknowledgement

Thanks so much of our consultants from Tbilisi State Medical University:

Professor Gaiane Simonia and Professor Nana Okrostsvaridze

Clinical trial identification

Legal entity responsible for the study

Tbilisi State Medical University and Institute for Personalized Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.