Vitamin D encouraged the growth of specific gut bacteria in mice that improve their immunity to cancer, according to a new study. The mice on a vitamin D-rich diet responded better to experimentally transplanted cancers and showed improved responses to immunotherapy treatment.
The effect remained when researchers used gene editing to remove a protein that binds to vitamin D in the blood and keeps it away from tissues.
The researchers found that vitamin D acts on the epithelial cells in the intestine, which increases the amount of Bacteroides fragilis bacteria, which limits the growth of transplanted tumors.
“What we’ve shown here came as a surprise — vitamin D can regulate the gut microbiome to favor a type of bacteria which gives mice better immunity to cancer,” says Caetano Reis e Sousa, senior author and head of the immunobiology laboratory at the Francis Crick Institute, US.
“This could one day be important for cancer treatment in humans, but we don’t know how and why vitamin D has this effect via the microbiome. More work is needed before we can conclusively say that correcting a vitamin D deficiency has benefits for cancer prevention or treatment.”
Vitamin D cancer link
The research was published in Science. It was conducted by a team from the Francis Crick Institute, the National Cancer Institute of the US National Institutes of Health and the Danish Aalborg University.
To determine whether the bacterial changes identified drove improved cancer immunity, the researchers provided mice on a regular diet with Bacteroides fragilis bacteria. These mice could also resist tumor growth better, but not when receiving a vitamin D-deficient diet.
Although studies have proposed a link between vitamin D deficiency and cancer risk, there is no conclusive evidence. The research team analyzed a dataset of 1.5 million people in Denmark, highlighting a link between lower vitamin D levels and increased cancer risk. Due to its northern latitude, Danish people generally have a lower rate of vitamin D synthesis through sunlight on the skin.
In addition, a cancer patient population analysis suggested that people with higher vitamin D levels were more likely to respond well to immune-based cancer treatments. Patients with a better vitamin D signature — the combination of activity in the body related to vitamin D — responded better to immune checkpoint therapy.
The study suggests vitamin D levels are a “potential determinant of cancer immunity and immunotherapy success.” In humans, research indicates that vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment, immunity to cancer and increased overall survival.
The researchers caution that more work is needed to conclusively determine vitamin D’s impact on cancer.Impact on humans
Bacteroides fragilis bacteria are also found in human gut microbiomes. Still, more research is needed to understand whether vitamin D helps provide immune resistance to cancer through the mechanism identified in mice.
“These findings contribute to the growing body of knowledge on the role of microbiota in cancer immunity and the potential of dietary interventions to fine-tune this relationship for improved patient outcomes,” underscores Romina Goldszmid, Stadtman investigator in the National Cancer Institute’s Center For Cancer Research
“However, further research is warranted to fully understand the underlying mechanisms and how they can be harnessed to develop personalized treatment strategies.”
Similarly, Evangelos Giampazolias, a former postdoctoral researcher at the Francis Crick Institute, highlights the challenge of pinpointing the factors distinguishing a “good” from a “bad” microbiome.
“A key question we are currently trying to answer is how exactly vitamin D supports a ‘good’ microbiome. If we can answer this, we might uncover new ways the microbiome influences the immune system, potentially offering exciting possibilities in preventing or treating cancer.”
The “sunshine” nutrient
Research has linked vitamin D to various health benefits. For example, low levels of the sunshine nutrient were associated with an increased risk of Long COVID in a study published last year.
Meanwhile, taking vitamin D supplements may decrease the risk of prediabetic adults developing diabetes by 15%.
At the same time, researchers question the curative effect of vitamin D on kids’ bone health, dispelling that the supplements prevent fractures or improve bone strength.
Dr. Nisharnthi Duggan, research information manager at Cancer Research UK, comments: “We know that vitamin D deficiency can cause health problems. However, there isn’t enough evidence to link vitamin D levels to cancer risk. This early-stage research in mice, coupled with an analysis of Danish population data, seeks to address the evidence gap.”
“A bit of sunlight can help our bodies make vitamin D, but you don’t need to sunbathe to boost this process. Most people in the UK can make enough vitamin D by spending short periods in the summer sun.”
She concludes: “We can also get vitamin D from our diet and supplements. We know that staying safe in the sun can reduce cancer risk, so seek shade, cover up and apply sunscreen when the sun is strong.”