Probiotics Protect Intestine Lining from Radiation Damage

The research was published online November 2011 in the journal Gut.

Radiation therapy frequently is used to treat prostate, cervical, bladder, endometrial, and other abdominal cancers. But the therapy can destroy both cancer cells and healthy ones, leading to severe bouts of diarrhea if the lining of the intestine gets damaged. “For many patients, this means radiation therapy must be discontinued, or the radiation dose reduced, while the intestine heals,” said senior investigator William F. Stenson, MD, a professor of gastroenterology and inflammatory bowel disease at the Washington University School of Medicine in St. Louis (MO, USA). “Probiotics may provide a way to protect the lining of the small intestine from some of that damage.”

Dr. Stenson has been looking for ways to repair and protect healthy tissue from radiation. This study showed that the probiotic bacteria Lactobacillus rhamnosus GG (LGG), among other Lactobacillus probiotic strains, protected the lining of the small intestine in mice receiving radiation. “The lining of the intestine is only one cell-layer thick,” Dr. Stenson stated. “This layer of epithelial cells separates the rest of the body from what's inside the intestine. If the epithelium breaks down as the result of radiation, the bacteria that normally reside in the intestine can be released, travel through the body and cause serious problems such as sepsis.”

The researchers found that the probiotic was effective only if administered to mice before radiation exposure. If the mice received the probiotic after damage to the intestinal lining had occurred, the LGG treatment could not repair it in this model.

Because the probiotic protected intestinal cells in mice exposed, the investigators believe it may be time to study probiotic use in patients receiving radiation therapy for abdominal cancers. “In earlier human studies, patients usually took a probiotic after diarrhea developed when the cells in the intestine already were injured,” remarked first author Matthew A. Ciorba, MD, assistant professor of medicine in the division of gastroenterology. “Our study suggests we should give the probiotic prior to the onset of symptoms, or even before the initiation of radiation because, at least in this scenario, the key function of the probiotic seems to be preventing damage, rather than facilitating repair.”

The investigators sought to assess LGG’s protective effects in a way that would leave little doubt about whether it was preventing injury, and if so, how it was protecting the cells that line the intestine. “Some human studies have looked at the possibility that probiotics might reduce diarrhea, but most of those studies have not been quite as rigorous as we would like, and the mechanism by which the probiotics might work has not been addressed,” Dr. Stenson said.

Earlier, Dr. Stenson and his colleagues demonstrated that a molecular pathway involving prostaglandins and cyclooxygenase-2 (COX-2), major components in inflammation, could protect cells in the small intestine by preventing apoptosis that occurs in response to radiation. They gave measured doses of LGG to mice, directly delivering the live bacteria to the stomach. They discovered it protected only mice that could make COX-2. In mutant mice unable to manufacture COX-2, the radiation destroyed epithelial cells in the intestine, just as it did in mice that did not receive the probiotic.

“In the large intestine, or colon, cells that make COX-2 migrate to sites of injury and assist in repair,” Dr. Ciorba stated. “In this study, we evaluated that response in the small intestine, and we found that COX-2-expressing cells could migrate from the lining to the area of the intestine, called the crypt, where new epithelial cells are made, and we believe this mechanism is key to the protective effect we observed.”

If human studies are initiated, Dr. Ciorba reported on one bit of promising news is that the doses of probiotic given to mice were not very large, and their intestines were protected. Therefore, people would not require huge doses of the probiotic to get protection. “The bacteria we use are similar to what’s found in yogurt or in commercially available probiotics,” he said. “So theoretically, there shouldn’t be risk associated with this preventative treatment strategy any more than there would be in a patient with abdominal cancer eating yogurt.”

Moreover, Dr. Ciorba noted, planned research is focused on isolating the specific radioprotective factor produced by the probiotic. When that is identified, a therapeutic could be developed to exploit the probiotic benefit without using the live bacteria.

Related Links:
Washington University School of Medicine in St. Louis