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Cancer researchers think they have found an explanation for why some cancer drugs don’t always work. The answer — and a possible solution — may be found in the gut microbiome.
The composition of a person’s gut microbiome — which consists of trillions of bacteria and other microbes — appears to influence whether a ground-breaking cancer treatment called immunotherapy is successful in some patients. Scientists have found that patients who harbor certain gut bacteria have better responses to immunotherapy than patients who lack them.
Even more stunning: scientists believe that giving patients a fiber-rich diet of fruits, vegetables, beans, nuts and whole grains to nourish the microbiome might improve the odds that the cancer treatment is effective.
A clinical trial testing the theory is currently underway at the University of Texas MD Anderson Cancer Center in Houston, the largest cancer center in the United States.
It includes participants like Hector Facton, a pediatrician in San Angelo who is undergoing immunotherapy treatments for Stage 4 melanoma.
“I’m eating triple the amount of fruits and vegetables that I used to eat,” Facton said. “I eat healthy, but not to the levels that I am now. A huge portion of my plate is always vegetables, lots of quinoa — anything I can find that has fiber in it.”
Scientists caution that this strategy of using a fiber-rich diet — or any diet for that matter — to boost immunotherapy remains unproven. But the research they are doing is shedding new light on how the gut microbiome affects our ability to fight disease.
“My patients who are starting treatment often ask if there’s something else they could be doing to enhance their chances of responding to immunotherapy,” said Jennifer McQuade, an assistant professor and physician scientist in melanoma medical oncology at MD Anderson. “We’re trying to test this diet with the same rigor that we use to test drugs.”
Manipulating the microbiome
Scientists have long known that the microbiome is a crucial part of our immune systems. By some estimates, between 60 and 80 percent of the immune cells in our bodies reside in the gut.
But only recently did it become apparent that these microbes might affect cancer outcomes. Scientists at the University of Chicago discovered that mice with a strain of gut bacteria known as Bifidobacterium had a stronger immune response against melanoma tumors than mice who lacked the bacteria. They found that giving Bifidobacterium to the deficient mice slowed tumor growth. What’s more, combining the bacteria with an immunotherapy drug known as a checkpoint inhibitor nearly abolished the tumors.
Human studies showed that these checkpoint inhibitors were also more effective in cancer patients whose guts had more microbial diversity, as well as a greater abundance of several microbes, including Akkermansia muciniphila and Bifidobacterium longum. Patients with low levels of these and other microbes were less likely to respond to the treatment.
Some researchers are trying to overcome resistance to immunotherapy by doing fecal transplants. They take stool samples teeming with gut microbes from patients who responded to the drugs and transfer it via colonoscopy to another patient. In one recent trial, scientists gave fecal transplants to 15 people with advanced melanoma who didn’t respond to immunotherapy.
Based on their histories, the 15 patients had a less than 10 percent likelihood of responding to immunotherapy. But after undergoing stool transplants, six patients began responding to the drugs. Hassane Zarour, a cancer immunologist who led the study, called it “an encouraging proof of principle,” and said he is now recruiting melanoma and lung cancer patients for a larger study.
“We don’t want to say that the microbiome is the only mechanism,” said Zarour, the co-leader of the Cancer Immunology and Immunotherapy Program at the University of Pittsburgh Medical Center. “But we have learned that the microbiome could definitely be responsible for the inability of some patients to respond.”
Zarour said the goal of his work is to figure out which gut microbes are involved and then package them into pills that patients could take to alter their microbiomes. “The endgame is not fecal transplants,” he added. “Giving patients a cocktail of probiotics might be the best option.”
Studying a fiber-rich diet
Meanwhile at MD Anderson, McQuade and her colleague Jennifer Wargo, a cancer surgeon, explored a different route: why not change patients’ microbiomes by changing what they eat?
McQuade pointed out that some of the gut microbes that appear to improve how patients respond to immunotherapy are known to thrive on fiber. “These are bacteria that help us break down and utilize starch and fibers,” she said.
The team examined the diets of 128 melanoma patients and found that those who regularly ate large amounts of fiber from fruits, vegetables, and other plant foods had better outcomes on immunotherapy than patients who ate the least amount of fiber. Their findings, published in Science in December, showed that every five-gram increase in daily fiber intake was associated with a 30 percent lower risk of death or cancer progression.
In the new study, patients are given daily meals that include as much as 50 grams of daily fiber from foods like beans, lentils, farro, brown rice, fruits, and vegetables — about twice the recommended amount. The average American only eats about half that amount, roughly 15 grams. (A control group will eat a healthy diet that follows guidelines from the American Cancer Society.)
Facton in San Angelo was diagnosed in November 2021 with melanoma that had spread to his lymph nodes after his wife noticed a golf-ball sized lump on his back. He began immunotherapy and enrolled in three-month the diet trial.
“It was huge servings, like a plate heaping with broccoli or quinoa, or mixed vegetables,” he said. “It was an impressive amount — more than I have ever eaten in one serving.”
In January, he underwent surgery and learned the tumor was gone. “There was just a bunch of scar tissue there,” he said. “There was no cancer to be found.”
Facton is continuing immunotherapy for nine months, and he’s decided to continue his new way of eating. “I feel better, and I don’t see any downside to it,” he said. “It makes me a healthier person overall — and now, cancer free. What a huge bonus.”
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