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Published on: October 13, 2023
Modulation of colon cancer by nutmeg
Fei Li1,2, Xiu-Wei Yang3, Kristopher W Krausz1
1†Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
Abstract:
Colon cancer is the most common cancer and the third leading cause of cancer mortality in humans. Using mass spectrometry-based metabolomics, the current study revealed the accumulation of four uremic toxins (cresol sulfate, cresol glucuronide, indoxyl sulfate, and phenyl sulfate) in the serum of mice harboring adenomatous polyposis coli (APC) gene mutation-induced colon cancer. These uremic toxins, likely generated from the gut microbiota, were associated with an increase in the expression of the proinflammatory cytokine IL-6 and a disorder of lipid metabolism. Nutmeg, which exhibits antimicrobial activity, attenuated the levels of uremic toxins and decreased intestinal tumorigenesis in Apc(min/+) mice. Nutmeg-treated Apc(min/+) mice had decreased IL-6 levels and normalized dysregulated lipid metabolism, suggesting that uremic toxins are responsible, in part, for the metabolic disorders that occur during tumorigenesis. These studies demonstrate a potential biochemical link among gut microbial metabolism, inflammation, and metabolic disorders and suggest that modulation of gut microbiota and lipid metabolism using dietary intervention or drugs may be effective in colon cancer chemoprevention strategies.
Insights
This study links gut microbial-produced uremic toxins to colon cancer development, inflammation, and lipid disorders. Nutmeg supplementation reduced these toxins, decreasing tumor growth and improving metabolic health in mice.
Area of Science:
- Biochemistry
- Oncology
- Microbiology
Background:
- Colon cancer is a leading cause of cancer mortality.
- Gut microbiota plays a role in cancer development.
- Uremic toxins are implicated in metabolic disorders.
Purpose of the Study:
- To investigate the role of uremic toxins in colon cancer.
- To explore the effects of nutmeg on uremic toxins and tumorigenesis.
- To understand the link between gut microbiota, inflammation, and lipid metabolism in colon cancer.
Main Methods:
- Mass spectrometry-based metabolomics in Apc(min/+) mice.
- Analysis of uremic toxin levels, IL-6 expression, and lipid metabolism.
- Evaluation of nutmeg's effects on tumorigenesis and metabolic markers.
Main Results:
- Four uremic toxins (cresol sulfate, cresol glucuronide, indoxyl sulfate, phenyl sulfate) accumulated in colon cancer mice.
- These toxins correlated with increased IL-6 and lipid metabolism disorders.
- Nutmeg treatment reduced uremic toxins, IL-6, and intestinal tumors, normalizing lipid metabolism.
Conclusions:
- Uremic toxins contribute to inflammation and metabolic dysfunction in colon cancer.
- Nutmeg shows potential for colon cancer chemoprevention by modulating gut microbiota and lipid metabolism.
- Targeting gut microbiota and lipid metabolism offers a strategy for colon cancer prevention.
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