Fasting and a gut bacterium together prime the intestine to recover from radiation

A 24-hour fast can prepare the small intestine to regenerate after radiation damage, but only when a specific gut bacterium, Akkermansia muciniphila, is present. The preclinical study, from The University of Texas MD Anderson Cancer Center, identifies a chain of events linking diet, the microbiome and gene regulation in intestinal cells. It was published in Proceedings of the National Academy of Sciences.

The clinical problem

Radiation therapy is widely used for abdominal cancers, including pancreatic, colorectal and gynaecologic tumours. The lining of the small intestine is highly sensitive to radiation. When it is injured, patients can develop nausea, diarrhoea and infections, and severe damage can be life-threatening. The risk of such injury can also limit the dose that clinicians are able to deliver.

Earlier work from the laboratory of Helen Piwnica-Worms had shown in preclinical models that fasting before radiation helped the intestine recover. What remained unclear was why going without food had this effect.

A microbiome-to-chromatin pathway

The new study, co-led by Piwnica-Worms (Experimental Radiation Oncology) and Kunal Rai (Genomic Medicine), found that 24 hours of fasting increased the abundance of A. muciniphila in the small intestine. The bacterium produces propionate, a short-chain fatty acid.

According to the researchers, propionate acts together with other metabolic changes caused by fasting to alter histones, the proteins around which DNA is packaged. Chemical marks on histones can change which genes are active without altering the DNA sequence. Here, the changes made regions of DNA more accessible, allowing genes involved in tissue regeneration to be switched on. Fasting also increased the number of intestinal cells carrying these repair programmes.

When radiation later struck, these primed cells could expand and help rebuild the damaged lining. The authors describe the pathway as a microbiome-metabolite-chromatin axis, a phrase that also appears in the paper's title.

The bacterium is necessary, but not sufficient alone

To test how much the bacterium mattered, the team selectively removed it. Without A. muciniphila, fasting no longer produced the same regenerative benefit. The protective response returned only when the bacterium was restored and the animals also fasted, indicating that neither fasting nor the microbe alone reproduced the full effect.

This suggests that fasting does more than briefly alter gut metabolism. In combination with the microbe, it appears to set intestinal cells into a state that supports faster recovery after injury.

Limitations and next steps

The work is preclinical, and the source does not report human data. It remains unknown whether the same mechanism operates in people or whether it could safely improve outcomes for patients receiving radiation. The study also does not establish that fasting itself would be advisable during cancer treatment.

The researchers see several possible directions if further studies hold up:

• Testing whether the pathway protects other rapidly dividing tissues, such as bone marrow, which can also be damaged by cancer therapy.
• Exploring clinical trials of this repair mechanism in patients undergoing abdominal radiation.
• Developing ways to reproduce the effect without fasting, for example through beneficial bacteria or the molecules they make.

Rai noted that fasting is not always practical for people with cancer, and that dietary measures, targeted microbes or their metabolites could all be routes to the same end. For researchers, the study offers a defined molecular route from a dietary intervention to cell-state change, which could guide work on microbiome-based radioprotection.

The study was funded by the National Cancer Institute at the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. The first author is Praveen Barrodia, with Robert R. Jenq among the co-authors.

Source: A 24-hour fast triggers a surprising repair response in the gut (ScienceDaily: health and medicine, 8 November 2026).

Image: AI-generated illustration.