A 24-hour fast can help prepare the intestines to recover from radiation damage, but scientists have discovered that a particular gut bacteria plays a crucial role in making this possible. New preclinical research from the University of Texas MD Anderson Cancer Center reveals how fasting and beneficial microbes work together to activate the body’s natural tissue repair mechanisms.
The findings could eventually lead to new ways to protect healthy tissues during cancer treatment. By improving the gut’s ability to recover from radiation exposure, researchers hope to reduce serious side effects and potentially make radiation therapy safer and more effective.
Published in the Proceedings of the National Academy of SciencesThe study was co-led by Helen Piwnica-Worms, Ph.D., professor of experimental radiation oncology, and Kunal Rai, Ph.D., professor of genomic medicine.
“Fasting helps prepare intestinal cells to respond more quickly and effectively after injury, almost like training the cells with an emergency preparedness plan,” Piwnica-Worms said. “This study helps explain how this plan is organized and identifies a key bacteria involved in coordinating the response.”
Why radiotherapy can damage the intestines
Radiation therapy is widely used to treat abdominal cancers, including pancreatic, colorectal, and gynecologic cancers. Although radiation can destroy cancer cells, it can also damage nearby healthy tissue. The small intestine is particularly vulnerable because its delicate lining is very sensitive to radiation exposure.
When this protective wall is damaged, patients may experience nausea, diarrhea and infections. Serious injuries can lead to life-threatening complications. These risks can also limit the amount of radiation therapy that doctors can safely administer, potentially limiting treatment options.
Previous preclinical research from the Piwnica-Worms lab showed that fasting before radiation exposure helped the intestines recover afterward. However, researchers had not yet completely determined why starving yourself produced this protective effect.
The latest study provides an important piece of this puzzle by identifying a specific gut bacteria and explaining how it helps gut cells prepare for injury.
How a 24-hour fast activates intestinal repair
Researchers found that 24 hours of fasting increased the abundance of a beneficial bacteria called Akkermansia muciniphilaalso known as AKK, in the small intestine. This microbe produces a substance called propionate, which helps trigger changes inside intestinal cells that better prepare them to regenerate following radiation damage.
Propionate works alongside other metabolic changes caused by fasting to modify proteins called histones. These proteins serve as the structures around which DNA is packaged inside cells. Small chemical markers added to histones can influence which genes become active without changing the underlying DNA sequence.
These modifications make portions of DNA more accessible, allowing cells to activate genes involved in tissue regeneration. During fasting, a population of intestinal cells carrying these repair programs becomes more abundant.
This is because fasting helps prepare these cells for the biological instructions they will need in the event of injury. When the intestines are then exposed to radiation, the prepared cells can grow and help rebuild the damaged intestinal lining.
Gut bacteria found to be key to recovery
To determine the importance of AKK in this process, the researchers selectively eliminated the bacteria. Without it, fasting no longer produced the same regenerative benefits.
Even more telling, the protective response only returned when the bacteria was restored in combination with fasting. This demonstrated that neither component was sufficient on its own to reproduce the full effect observed in the study.
The results suggest that fasting does more than temporarily alter gut metabolism. With AKK, it modifies the activity of intestinal cells before exposure to radiation, placing them in a state that allows for more efficient recovery after damage occurs.
By discovering this link between nutrition, gut bacteria and cell regeneration, researchers have identified a potential new way to strengthen the body’s response to tissue damage. This discovery could be particularly useful in protecting healthy organs during cancer treatment.
Could gut bacteria make cancer treatment safer?
Although the results are promising, the research remains preclinical. Additional studies will be needed to determine whether the same protective mechanism works in humans and whether it can safely improve outcomes for patients receiving radiation therapy.
One possibility is that the newly discovered pathway could be used to help other healthy tissues recover from cancer treatment. Researchers are particularly interested in tissues containing rapidly dividing cells, including bone marrow, which can also suffer treatment-related damage.
If further research confirms these findings, clinical trials could eventually determine whether activating this repair mechanism benefits patients undergoing abdominal radiation therapy.
Importantly, this discovery could also provide ways to achieve these effects without requiring patients to fast. Treatments involving beneficial bacteria or the molecules they produce could potentially stimulate similar repair processes while avoiding the practical difficulties of dietary restriction during cancer care.
“Fasting is not always practical for cancer patients, and this work supports several other potential ways to improve recovery after treatment,” Rai said. “Whether through dietary interventions, targeted microbes or their metabolites, the goal is to help repair healthy tissues more effectively while patients receive the cancer treatments they need.”
The research was funded by the National Cancer Institute (NCI) within the National Institutes of Health (NIH) and the Cancer Prevention and Research Institute of Texas (CPRIT).
Gn Health
