Could fasting help people treated for gastrointestinal cancer?

Intestinal stem cells from mice that fasted for 24 hours,
at right, produced much more substantial intestinal
organoids than stem cells from mice that did not fast,
at left. Photo courtesy MIT taken by Maria Mihaylova
and Chia-Wei Cheng

CANCER DIGEST – May 12, 2018 – In a study in mice, researchers at MIT in Boston have found that fasting caused stem cells in the animals become more regenerative. The researchers also found that they could boost regeneration with a molecule that activates the same metabolic switch.

The study published in the May 3, 2018 issue of the journal Cell Stem Cell, showed that fasting causes cells in the intestine to switch from their usual metabolism, which burns carbohydrates such as sugars, to metabolizing fatty acids. This switch occurs through activation of genetic switches called transcription factors.

Intestinal stem cells are responsible for maintaining the lining of the intestine, which typically renews itself every five days. When injured or infected, it is the stem cells that repair the damage. As people age, these intestinal stem cells lose their regenerative ability, which slows the repair and renewal of the intestinal lining.

In the study, the researchers compared the intestinal stem cells of mice that had fasted for 24 hour to cells of mice that had eaten normally. They grew the cells in a culture dish to see if the cells could grow into "mini-intestines" known as organoids. They found that stem cells of the fasting mice doubled their regenerative capacity compared to the non-fasting mice. They repeated the test in both young and old mice and found similar rates of doubling in the fasting mice compared to non-fasting mice.

"Fasting has many effects in the intestine, which include boosting regeneration as well as potential uses in any type of ailment that impinges on the intestine, such as infections or cancers," says Omer Yilmaz, an MIT assistant professor of biology and senior author of the study.

In addition to fasting the researchers showed that they could mimic the effects of fasting by treating the mice with a molecule that acts like the transcription factors that switch on the stem cell regeneration process. This suggests that a drug might be developed to stimulate intestinal stem cell regeneration without requiring fasting.

The researchers suggest that one group that could benefit from such treatment is cancer patients who are receiving chemotherapy, which often harms intestinal cells. It could also benefit older people who experience intestinal infections or other gastrointestinal disorders that can damage the lining of the intestine.

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