Patients' Gut Bugs May Play Role in Cancer Care
THURSDAY, Nov. 2, 2017 -- The type of bacteria that cancer patients harbor in the gut might affect their odds of responding to certain treatments, two early studies hint.
The research, in humans and mice, adds to evidence that gut bacteria play a key role in the immune system.
But experts stressed it's too soon to make recommendations to cancer patients -- including whether they should take "probiotic" supplements.
Both studies looked at whether there's a link between patients' gut bacteria and their responses to newer cancer drugs called PD-1 inhibitors. The drugs, which include Keytruda (pembrolizumab) and Opdivo (nivolumab), work by freeing up the immune system to attack cancer cells.
The drugs are approved for several cancers, including advanced cases of melanoma, lung, bladder and stomach cancers.
In one study, researchers focused on 112 patients with advanced melanoma, the deadliest form of skin cancer. The investigators found that those who'd responded to PD-1 therapy tended to have a gut "microbiome" that was distinct from those of patients who did not respond.
Those who'd responded generally had more diversity in their bacteria, plus higher concentrations of common bacteria called Ruminococcus and Faecalibacterium.
Still, the researchers said the findings do not prove that those bacteria improve the odds of doing well on PD-1 therapy.
"Only a clinical trial can show that. This needs to be tested," said senior researcher Dr. Jennifer Wargo, an associate professor at University of Texas M.D. Anderson Cancer Center in Houston.
However, the findings build on evidence of a "clear link between the gut microbiome and immune function," she said.
The "microbiome" refers to the trillions of bacteria and other microbes that dwell in the human body.
Studies have found that the diversity of those bugs -- particularly in the gut -- is linked to the risks of various health conditions, including those related to immune function.
In general, studies have found, the more diversity in the gut microbiome, the better.
Wargo's study involved a group of melanoma patients who'd responded to a PD-1 inhibitor -- meaning their cancer had stabilized or regressed for at least six months -- and a group that did not respond.
Overall, the responders showed an "abundance" of Ruminococcus and Faecalibacterium. In contrast, the non-responders had a high concentration of Bacteroidales bacteria.
To test whether the microbes might have a direct influence on treatment response, the researchers transplanted gut bacteria from the patients into lab mice.
Those animals also responded better to PD-1 therapy, versus mice that had transplants from non-responding patients, according to the report.
In the second study, French researchers focused on 249 patients treated with a PD-1 inhibitor for lung, kidney or urinary tract cancers. Just over one-quarter had taken antibiotics to treat an infection shortly before or after starting PD-1 treatment. (Antibiotics are drugs that kill bacteria).
Overall, those antibiotic patients had lower survival odds. Plus, 69 percent of patients who responded to PD-1 treatment had detectable amounts of bacteria called Akkermansia muciniphila, versus 34 percent of patients who did not respond.
It all raises "exciting possibilities," Wargo said. Namely, could manipulating the gut microbiome improve the chances of responding to cancer treatment?
But there are plenty of unanswered questions. For one, "We don't really know what constitutes a 'favorable' microbiome," Wargo noted. So there is no way to tell cancer patients whether any probiotic might benefit them.
In fact, she said, if patients were to take a random supplement, it might end up causing harm. In addition, there also needs to be more research into gut bacteria and responses to other cancer therapies, Wargo added.
Dr. Nikhil Khushalani specializes in treating skin cancer at Moffitt Cancer Center, in Tampa, Fla. He cautioned that the study findings are a "first step," but also a "very intriguing" one.
Khushalani said the findings raise the possibility of testing patients' stool samples to see who has a greater likelihood of responding to PD-1 therapy. "That could help us in truly tailoring treatment," he suggested.
Then there's the possibility of actually altering patients' microbiomes -- whether through probiotics or even fecal transplants, Khushalani added.
Like Wargo, he cautioned patients against self-treating with probiotics, given the unknowns.
"But that could be where we're heading," Khushalani said. "Hopefully, this will open the door to even more research in this arena."
The new research appears in the Nov. 3 issue of Science.
The American Cancer Society has more on cancer immunotherapy.
Posted: November 2017