A 24-hour fast altered the gut microbiome and helped the small intestine recover from radiation damage in mice, according to research that may offer clues for reducing the gastrointestinal side effects of cancer treatment.
The findings are preclinical and do not establish that fasting is safe or beneficial for people receiving radiation therapy. Cancer patients can be especially vulnerable to poor appetite, weight loss and malnutrition, and they should not fast or make significant dietary changes during treatment without guidance from their oncology team.
Published in the Proceedings of the National Academy of Sciences, the study focused on Akkermansia muciniphila, a bacterium commonly found in the gut. Researchers at The University of Texas MD Anderson Cancer Center found that fasting increased levels of the bacterium in the small intestines of mice and appeared to prepare certain intestinal cells to respond more effectively after radiation injury.
Radiation therapy is used to treat several cancers in the abdominal and pelvic regions, including pancreatic, colorectal and gynecologic cancers. Because the small intestine is sensitive to radiation, treatment can damage its rapidly renewing lining and contribute to nausea, diarrhea, infection and other complications.
Previous animal research had suggested that fasting before radiation could improve intestinal recovery. The new study was designed to investigate why that might happen and whether gut microbes were involved.
“Fasting helps prepare intestinal cells to respond more quickly and effectively after injury, almost like training the cells with an emergency preparedness plan,” said Helen Piwnica-Worms, a professor of experimental radiation oncology at MD Anderson. “This study helps explain how that plan is organized and identifies a key bacterium involved in coordinating the response.”
Researchers found that fasting increased Akkermansia muciniphila, sometimes shortened to AKK, in the small intestine. The bacterium produces propionate, a short-chain fatty acid created when microbes break down certain substances in the gut.
Propionate appeared to work alongside other metabolic changes caused by fasting to modify histones, proteins around which DNA is wrapped. These modifications did not change the cells’ genetic code. Instead, they influenced how easily certain genes could be activated.
The researchers identified a group of intestinal cells that accumulated during fasting and carried gene activity associated with tissue regeneration. After radiation exposure, those cells expanded and contributed to rebuilding the intestinal lining.
The study went beyond showing that fasting and AKK appeared at the same time. When researchers selectively removed the bacterium, fasting no longer produced the same regenerative response. When AKK was restored alongside fasting, the response returned.
That suggests the bacterium played a necessary role in the process observed in the animals. It does not prove, however, that AKK supplements, propionate or fasting would have the same effect in people.
The research also did not show that fasting reduces radiation side effects, allows patients to receive higher radiation doses or improves cancer outcomes. Those questions would require carefully controlled human trials.
The researchers said the broader goal is to understand whether the pathway could eventually be used without requiring patients to fast. Possibilities might include therapies involving specific microbes, microbial compounds or other ways of reproducing the cellular response.
“Fasting is not always practical for cancer patients, and this work supports several other potential ways to enhance recovery after treatment,” said Kunal Rai, a professor of genomic medicine at MD Anderson. “Whether through dietary interventions, targeted microbes or their metabolites, the goal is to help repair healthy tissue more effectively while patients receive the cancer therapies they need.”
Future studies will need to determine whether the same biological pathway exists in humans and whether it can be influenced safely during cancer treatment. Researchers are also interested in whether similar mechanisms could support other rapidly dividing tissues, such as bone marrow, after treatment-related damage.
The research was supported by the National Cancer Institute within the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. Several MD Anderson core facilities used in the study also received NIH and National Cancer Institute support.
Study co-author Kunal Rai reported equity in Koshika Therapeutics, personal fees and equity in Jivanu Therapeutics, personal fees from Daiichi Sankyo and support from Cyclacel Inc. outside the submitted research. Co-author Robert R. Jenq reported receiving patent royalties from Seres Therapeutics, serving as an adviser to Nestlé and MaaT Pharma and serving on the scientific advisory board of Postbiotics Plus.