Vitamin D encourages mouse gut bacteria to improve cancer immunity

Mice given a diet rich in vitamin D had better immune resistance to experimentally transplanted cancers.

While the evidence hasn’t been conclusive, previous research has suggested a link between vitamin D deficiency and human cancer risk.

The researchers investigated this by analyzing a dataset from 1.5 million Denmark citizens. This revealed a connection between decreased vitamin D levels and an increased risk of cancer. According to a different examination of a patient group with the disease, individuals with greater vitamin D levels2 were also suggested to be more likely to benefit from immune-based cancer treatments.

More investigation is required to determine whether vitamin D contributes to some immunological resistance to cancer through the same method, even though Bacteroides fragilis is also present in the human microbiome.

Scientists from the National Cancer Institute (NCI) of the United States National Institutes of Health (NIH), the Francis Crick Institute, and Aalborg University in Denmark have discovered that vitamin D promotes the development of a particular kind of gut bacteria in mice that improves their resistance to cancer.

According to the researchers, mice fed a diet high in vitamin D showed enhanced immunological resistance against experimentally implanted tumors and increased responses to immunotherapy treatment. The removal of a protein that binds to vitamin D in the blood through gene editing also had this impact.

The group discovered, rather surprisingly, that vitamin D stimulates intestinal epithelial cells, boosting the population of a bacterium known as Bacteroides fragilis. The transplanted tumors in the mice showed less growth, suggesting that this bacterium improved their resistance to cancer. However, the exact mechanism is yet unknown.

Mice on a regular diet were given Bacteroides fragilis to see if the bacterium alone may improve cancer immunity. Additionally, these mice showed greater resistance to tumor formation; however, this did not hold true when the mice were fed a diet low in vitamin D.

Caetano Reis e Sousa, head of the Immunobiology Laboratory at the Crick and senior author, said: “What we’ve shown here came as a surprise—vitamin D can regulate the gut microbiome to favor a type of bacteria that gives mice better immunity to cancer.

“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.”

Evangelos Giampazolias, a former postdoctoral researcher at the Crick and now Group Leader of the Cancer Immunosurveillance Group at the Cancer Research UK Manchester Institute, said: “Pinpointing the factors that distinguish a ‘good’ from a ‘bad’ microbiome is a major challenge. We found that vitamin D helps gut bacteria elicit cancer immunity, improving the response to immunotherapy in mice.

“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 in which the microbiome influences the immune system, potentially offering exciting possibilities in preventing or treating cancer.”

Romina Goldszmid, Stadtman Investigator in NCI’s Center For Cancer Research, said: “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. However, further research is warranted to fully understand the underlying mechanisms and how they can be harnessed to develop personalized treatment strategies.”

Research Information Manager at Cancer Research UK, Dr Nisharnthi Duggan said: “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. While the findings suggest a possible link between vitamin D and immune responses to cancer, further research is needed to confirm this.

“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 of time in the summer sun. We can also get vitamin D from our diet and supplements. We know that staying safe in the sun can reduce the risk of cancer, so seek shade, cover up and apply sunscreen when the sun is strong.”

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