A 24-hour fast triggers a surprising repair response in the gut

A 24-hour fast may help prepare the intestines to recover from radiation damage, but scientists have discovered that a particular gut bacterium 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 tissue during cancer treatment. By improving the intestine'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 Sciences, the 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 that plan is organized and identifies a key bacterium involved in coordinating the response."

Why Radiation Therapy Can Damage the Intestines

Radiation therapy is widely used to treat cancers in the abdomen, including pancreatic, colorectal, and gynecologic cancers. Although radiation can destroy cancer cells, it can also harm nearby healthy tissue. The small intestine is particularly vulnerable because its delicate lining is highly sensitive to radiation exposure.

When this protective lining becomes damaged, patients may experience nausea, diarrhea, and infections. Severe injuries can cause life-threatening complications. These risks can also restrict the amount of radiation doctors can safely administer, potentially limiting treatment options.

Previous preclinical research from the Piwnica-Worms Laboratory showed that fasting before radiation exposure helped the intestines recover afterward. However, researchers had not fully determined why going without food produced this protective effect.

The latest study provides an important piece of that puzzle by identifying a specific gut bacterium and explaining how it helps intestinal cells prepare for injury.

How a 24-Hour Fast Activates Gut Repair

Researchers found that 24 hours of fasting increased the abundance of a beneficial bacterium called Akkermansia muciniphila, also known as AKK, in the small intestine. This microbe produces a substance called propionate, which helps trigger changes inside intestinal cells that make them better prepared to regenerate following radiation damage.

Propionate works alongside other metabolic changes caused by fasting to modify proteins known as histones. These proteins serve as 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.

In effect, fasting helps prepare these cells with the biological instructions they will need if an injury occurs. When the intestines are subsequently exposed to radiation, the prepared cells can expand and help rebuild the damaged intestinal lining.

One Gut Bacterium Proves Essential for Recovery

To determine how important AKK was to this process, the researchers selectively removed the bacterium. Without it, fasting no longer produced the same regenerative benefits.

Even more revealing, the protective response returned only when the bacterium was restored in combination with fasting. This demonstrated that neither component alone was sufficient to reproduce the full effect observed in the study.

The results suggest that fasting does more than temporarily change the gut's metabolism. Together with AKK, it alters the activity of intestinal cells before radiation exposure, placing them in a state that supports more efficient recovery after damage occurs.

By uncovering this connection between nutrition, gut bacteria, and cellular regeneration, the researchers have identified a potential new way to strengthen the body's response to tissue injury. The discovery could be especially valuable for 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 operates 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 with rapidly dividing cells, including bone marrow, which can also suffer treatment-related damage.

If further investigations support the findings, clinical trials could eventually explore whether activating this repair mechanism benefits patients undergoing abdominal radiation therapy.

Importantly, the discovery may 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 food restriction during cancer care.

"Fasting is not always practical for cancer patients, and this work supports several other potential ways to enhance recovery after treatment," Rai said. "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."

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).