Fecal transplants, already being studied as a treatment for colon infections and type 2 diabetes, could also help the body fight cancer, according to new U.S. government-funded research. In a small clinical trial, some patients with advanced cancer who received the transplants began to respond to treatments that had not worked before, that stabilized or shrunk their tumors.
The purpose of a fecal transplant is to use the feces of a donor to repair someone’s gut microbiome, the environment of bacteria that lives along our digestive tract. The intestinal microbiome helps the body regulate everything from metabolism to a well-functioning immune system, and it is suspected that an unbalanced microbiome can increase or increase the risk of many health problems, such as diabetes, inflammatory bowel disease and certain infections. By sowing their digestive tract with the bacteria from the stool of a donor, it appears possible to cultivate a healthier intestinal microbiome.
Fecal microbiota transplantation (FMT) is currently only considered as an effective treatment for recurrent gastrointestinal infections caused by Clostridioides difficult, which can be fatal. But there are ongoing trials testing its use for other conditions. This new study, led by researchers from the National Cancer Institute, viewed FMT as a kind of stimulant for another emerging treatment, cancer immunotherapy.
Immunotherapy uses drugs to boost the immune system’s ability to detect cancer cells. These drugs contain immune control inhibitors, which remove the natural limiter that some cancers use to prevent detection by T cells. Although immune control inhibitors have shown great promise in the treatment of advanced forms of cancer, the tumors of some people are still resistant to suppression by the immune system, even after treatment. Some researchers have the theory that repairing the intestinal microbiome of these patients will also cause these tumors to become vulnerable to immunotherapy.
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“Cancer therapies are often dependent on stimulation of immune responses against tumors, which increases the possibility that the intestinal microbiota may influence the responses to the cancer via the immune system.” for cancer research, told Gizmodo by email.
The study involved 15 patients with advanced melanoma, the deadliest form of skin cancer, who had not previously responded to treatment with immune-control inhibitors. These patients received transplants from other patients with advanced melanoma who responded to therapy (often patients receive first a dose of antibiotics to clear up their existing microbiome, but not in this study). The donor stool was examined for potentially dangerous germs – a precaution that has become standard in the wake up of several diseases and one death associated with fecal transplants carrying drug-resistant bacteria in 2019.
Thereafter, six out of the 15 patients began to respond to the treatment. In one patient, their tumors shrank and counted for more than two years, while four others allowed their cancer to stabilize, with no signs of disease progression for at least more than a year. (It appears that the sixth patient responds fully to immunotherapy, but dies shortly after treatment from complications of an unrelated operation.)
“In these patients, the tumor progressed rapidly and life expectancy was short,” Trinchieri noted. “Stable diseases and shrinkage of the tumors will represent a significant improvement in the survival and quality of life of patients, and may lead to long-term survival and in some cases even cure.”
Both the intestinal microbiome and the immune system of these patients also showed signs that they changed favorably after the transplant, which allowed a better response to the treatment. And the transplants themselves are well tolerated, although the immunotherapy has probably caused mild side effects in some patients, including fatigue. The findings was published Thursday in the journal Science.
According to Trinchieri, the study is one of the first to show that altering the intestinal microbiome can improve a person’s response to immunotherapy. And while this is only evidence of the concept study, it also demonstrates the potential to target the microbiome in general for the treatment of cancer.
Despite this potential, more work needs to be done with larger groups of patients before poop transplants can become a standard of care for difficult cancer cases. The team’s research and others began to identify the types of bacteria that are likely to improve the immunotherapy response, as well as the patients who benefit most from a transplant. They also keep track of the patients who responded to FMT while using their donation for other studies.
In the future, this transplant technique – which requires a colonoscopy – may not even be the preferred method of delivery. Instead, Trinchieri said, we might just use a pill that contains the bacteria. Fortunately, some studies are already explore the method, as well as the use of FMT for other types of cancer.