*For medical professionals only
Vitamin D plays an important role in regulating immunity and symbiotic microorganisms, and many studies have discovered the mechanism of vitamin D against cancer, including reducing cancer cell proliferation, promoting apoptosis, reducing angiogenesis, and so on.
However, the relationship between vitamin D levels and cancer risk is not consistent in current clinical trials and epidemiological studies. Some studies support that higher blood levels of vitamin D or high dietary intake are associated with a reduced risk of morbidity/mortality from colorectal, breast, prostate, and pancreatic cancers.
Today, the scientific team of the Francis Crick Institute published an article in the journal Science, and researchers found that the vitamin acts directly on intestinal epithelial cells to promote the growth of Bacteroides fragilis by an unknown mechanism. Bacteroides fragilis is a known "anti-cancer bacterium" that can enhance anti-tumor immunity and enhance the effect of immunotherapy.
Diagram of the title of the dissertation
Vitamin D consists of two substances, vitamin D3 from foods of animal origin, vitamin D3 synthesized by the skin during sun exposure, and vitamin D2 from plants and fungi. Vitamin D is first metabolized by the liver to 25-hydroxyvitamin D (25-OHD), which is then converted to 1,25-(OH)2D in the kidneys, which binds to the vitamin D receptor (VDR) and regulates downstream gene expression.
Vitamin D-binding protein (Gc) is present in the blood, and Gc can bind to 25-OHD and 1,25-(OH)2D (collectively referred to as VitD) to store and balance calcium homeostasis in the blood.
Researchers began to focus on Gc because of another protein in the blood, sGCN. sGCN is involved in cleaving a receptor expressed by dendritic cells that is associated with antigen cross-presentation, inhibiting anti-tumor immunity and immunotherapy. Gc has a similar protein-binding domain that works with sGCN, leading researchers to speculate that Gc may also act as a barrier to anti-tumor responses.
The researchers knocked out the Gc in the mice and found that this significantly improved the immunity of the mice, and BrafV600E melanoma grew significantly slower than the control group, and they were more sensitive to immunotherapy.
Knockdown of Gc significantly enhanced anti-tumor immunity in mice
Further analysis found that vitamin D directly acted on VDR in intestinal epithelial cells, altered intestinal microbiota and enhanced anti-tumor immunity.
The researchers also found that this enhanced anti-tumor immunity could be "transmitted" through fecal transplantation (FMT), which required only an adequate supply of vitamin D, while antibiotic treatment reduced anti-tumor immunity in mice.
Obviously, there are intestinal bacteria here that are stirring up trouble.
The researchers analyzed the types and abundance of intestinal bacteria with different vitamin D availability and found that the abundance of Bacteroides fragilis increased significantly and the abundance of Prevosa breve decreased significantly at high vitamin D levels.
The results showed that high levels of Bacteroides fragilis could significantly improve the anti-tumor immunity of mice in the presence of adequate vitamin D.
Vitamin D + Bacteroides fragilis is the anti-cancer secret
Finally, the researchers analyzed the expression of VitD-VDR signaling in different cancers in the existing human database, and there was an association between low VitD-VDR and low survival and advanced disease in skin cancer, sarcoma, liver cancer, breast cancer, and prostate cancer.
The researchers also analyzed data from patients receiving immunotherapy for seven cancer types and found that low expression of VitD-VDR was associated with immunotherapy resistance and faster disease progression.
Overall, there is also an association between low VitD availability and low anti-tumor immunity in humans.
The association of VitD with cancer progression has also been observed in human databases
The good thing is that vitamin D supplementation is really easy and very cheap, and I hope that scientists will start clinical trials as soon as possible, if it can really help immunotherapy, it will be too meritorious.
Resources:
[1]https://www.science.org/doi/10.1126/science.adh7954?doi=10.1126/science.adh7954
[2]https://www.science.org/doi/10.1126/science.adp1309
The author of this article丨 Dai Siyu