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February 16, 2015
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Gut Reaction

Healthy gut bacteria may be needed for some cancer therapies to be effective.
BY Cheryl Alkon
PUBLISHED February 19, 2015
Can organisms that live in the human gut cause certain cancer treatments to be more effective? It looks that way, according to two research studies published in the November issue of Science.

The research on the human microbiome raises questions about the use of antibiotics—which can kill healthy gut bacteria—in patients being treated with immunotherapy and other anti-cancer drugs. It has also inspired researchers to ask whether good gut bacteria should be replaced in such patients, possibly via probiotics.

The microbiome refers to the collection of tiny organisms that live not only within the gut, but also in the mouth, skin and other body parts. In the digestive tract, the microbiome works to digest food and keep out foreign bacteria, a filter sometimes referred to as “the living shield,” says Stephanie Meyers, a nutritionist at Dana-Farber Cancer Institute in Boston, Mass. The microbiome can also metabolize several compounds in the gut which are then absorbed, so it has the potential to affect the body’s physiology.

In a study conducted by the National Cancer Institute, researchers looked at mice treated for cancers with immunotherapy. The treatment helped kill tumor cells in a group of the mice, about 70 percent of which were alive two months later. But in mice that took antibiotics before treatment, the immunotherapy was less effective — only 20 percent were alive at two months. Gut bacteria actually stimulated the treatment to work, the researchers found.

The team also demonstrated that oxaliplatin, a chemotherapy used to treat colorectal cancer, was less effective after antibiotics.

In a different study, this one conducted in France, researchers found that the chemotherapy drug cyclophosphamide works by making the gut microbiome leaky, allowing certain microbes to travel more deeply within the body, into the spleen and lymph nodes. When given antibiotics prior to treatment with cyclophosphamide, mice didn’t fare as well, because the microbes normally activated by the cancer treatment were not available, the scientists found.

But what does all this mean for human cancer treatment?

“It suggests the effect of the microbiota in determining response to cancer therapy may be quite broad,” says Giorgio Trinchieri, director of the Cancer and Inflammation Program at the Center for Cancer Research at the National Cancer Institute, and a co-author of the NCI study. However, “it is clearly too early to advise to withdraw antibiotic treatments in patients undergoing cancer therapy.” Ongoing studies, both his own and some in other National Institutes of Health laboratories, are exploring the connection between microbiota and their response to therapy, and may help researchers find answers.

The issue is not simply how much bacteria live in the microbiota, but what kinds of bacteria are there and in other areas, such as the mouth and the skin, he adds. “Cancer patients may have a lower diversity of gut bacteria, which may be an increased link to an inflammatory state that may favor tumor initiation and progression.”

What about taking probiotics—live substances that help build up the number of healthy bacteria in the body, and are found in foods such as yogurt, kefir and root vegetables? And would prebiotics, found in foods such as onions and garlic, help probiotics work more effectively?

Patients undergoing chemotherapy are at a higher risk of developing diarrhea as a side effect, says Meyers, so to help lessen the severity and frequency of that problem, she is already counseling patients to take probiotics and prebiotics, both in the diet as well as in dietary supplements. However, further research is needed to characterize and quantify this positive effect. For instance, a 2014 study of people who had undergone radiation for pelvic cancer after either chemotherapy or surgery found that moderate to severe diarrhea was less frequent in the patients who used probiotics. Yet those results were not statistically significant.

“In the realm of cancer, I talk about probiotics every day,” Meyers says. “While there isn’t hard science across the board, patients taking probiotics may notice a decrease in their symptoms with a probiotic supplement.”

Meyers agrees that it is too soon to counsel patients on whether pro- or prebiotics might make their cancer treatments work better, but it’s OK for patients to query their oncologists, or nutritionists familiar with cancer, on the issue.

“It’s too early to make a recommendation, but I’ve been working with cancer patients for a while, and I don’t think it’s too early to be answering patients’ questions in a thoughtful way,” Meyers says.
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