Now, my colleague Evangelos Giampazorias, now at Cancer Research UK’s Manchester Research Institute, has found that switching off the gene that gives instructions to make the aptly named vitamin D-binding protein increases the growth of skin cancer cells in mice. Reis e Sousa was intrigued when he discovered that .
But it was the next experiment, he says, “that really hit home.”
To ensure that their findings were not due to some abnormality in the laboratory environment, Reis e Sousa’s team tested mice with the disabled gene in the same cages as mice carrying fully functional versions. was bred.
Surprisingly, the cage-mates’ tumors also turned out to be slow growing. But why do tumors grow slower in normal mice when approached by more cancer-resistant animals?
The power of poop
Giampazourias and Reis e Sousa quickly realized that one explanation for this was that rats eat each other’s feces. It is thought that something in the poop must have been transferred from the mouse with the deactivated gene to the normal mouse that was caged with it.
To find out whether the effect was related to the gut microbes that live inside the genetically modified mice, Reis e Sousa’s team gave antibiotics to some of the mice that carried the inactivated gene. administered. When the mice lost their resistance to the cancer and lost their ability to transmit the cancer to their cage mates, it became clear that the gut bacteria in the mice’s feces were somehow slowing tumor growth. .
Vitamin D-binding proteins keep most of the vitamin D in the blood, Reis-e-Souza explains. “This reduces the amount of vitamin D that reaches the tissues of the body, including the lining of the intestines.”
Reis e Sousa’s team disabled the gene that codes for vitamin D-binding protein, which increased vitamin D levels and promoted the growth and presence of certain bacteria.Bacteroides fragilis—This is also common in the human colon. And those bacteria can stimulate the immune system, Reis-e-Souza explains.
Switching off the gene and increasing or adding more vitamin D to the diet of genetically normal mice Bacteroides fragilis All administrations into the mouse intestines had the same effect. More killer T cells attacked the tumor and slowed its growth.
As a result of these higher vitamin D levels, the mice responded better to immunotherapy.
