Fecal transplants, already studied as a treatment for colon infections and type 2 diabetes, may also help the body fight cancer, suggests new research funded by the United States government. In a small clinical trial, some patients with advanced cancer who received the transplants began to respond to treatments that did not work previously, which stabilized or reduced their tumors.
The purpose of a fecal transplant is to use a donor’s feces to restart a person’s intestinal microbiome, the neighborhood of bacteria that live along our digestive tract. The intestinal microbiome helps the body regulate everything from metabolism to a functioning immune system, and an imbalanced microbiome is believed to cause or increase the risk of many health problems, such as diabetes, inflammatory bowel diseases and certain infections. By sowing your digestive tract with bacteria from a donor’s feces, it seems possible to develop a healthier intestinal microbiome.
Fecal microbiota (FMT) transplantation is currently considered only an effective treatment for recurrent gastrointestinal infections caused by Clostridioides difficile, which can be fatal. But there are trials underway testing its use for other conditions. This new study was led by researchers from the Hillman Cancer Center at the University of Pittsburgh Medical Center, as well as scientists from the National Cancer Institute. They looked at FMT as a kind of booster for another emerging treatment, cancer immunotherapy.
Immunotherapy uses drugs to amplify the immune system’s ability to find and kill cancer cells. These drugs include immune checkpoint inhibitors, which remove the natural limiter that some types of cancer use to prevent detection by T cells. While immune checkpoint inhibitors have shown great promise in treating advanced forms of cancer, Some people’s tumors continue to resist suppression by the immune system, even after treatment. Some researchers theorized that redefining the intestinal microbiome of these patients will also make these tumors vulnerable to immunotherapy.
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“Cancer therapies often depend on stimulating anti-tumor immune responses, increasing the possibility that the intestinal microbiota may influence the host’s responses to cancer therapy through the immune system,” study author Giorgio Trinchieri, head of the Integrative Cancer Immunology at the NCI Center for Cancer Research, he told Gizmodo by email.
UPMC researchers treated 15 patients with advanced melanoma, the most lethal form of skin cancer, who had previously failed to respond to treatment with immune control point inhibitors. These patients received transplants from other patients with advanced melanoma who responded to therapy (patients often receive a dose of antibiotics first to help clean up the existing microbiome, but not in this study). The donor’s faeces were examined for any potentially dangerous germs – a precaution that has become standard in the awakening of various diseases and a death associated with fecal transplants with drug-resistant bacteria in 2019. The NCI helped analyze the microbiome samples from these patients.
Subsequently, six of the 15 patients began to respond to treatment. In one patient, the tumors continued to shrink for more than two years and increase, while another four had their cancer stabilized, with no signs of disease progression for at least more than a year. (The sixth patient appeared to respond completely to immunotherapy, but died shortly after treating complications from unrelated surgery.)
“In these patients, the tumor was progressing rapidly and life expectancy was short,” noted Trinchieri. “Stable disease and tumor reduction would represent a significant improvement in patient survival and quality of life and can result in long-term survival and, in some cases, healing.”
Both the intestinal microbiome and the immune system of these patients also showed signs of favorable change after transplantation, allowing for a better response to therapy. And the transplants themselves were well tolerated, although immunotherapy probably caused minor side effects in some patients, including fatigue. The discoveries were published in the journal Science on Thursday.
The study, according to Trinchieri, is one of the first to show that changing the intestinal microbiome can improve a person’s response to immunotherapy. And while this is just a proof-of-concept study, it also demonstrates the potential to target the microbiome in general for cancer treatment.
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. Research by the team and others is beginning to identify the types of bacteria most likely to improve the response to immunotherapy, as well as the patients most likely to benefit from a transplant. They are also monitoring patients who responded to FMT, while using their donated poop for other studies.
In the future, this transplantation technique – which requires a colonoscopy – may not even be the preferred method of delivery. Instead, Trinchieri said, perhaps we could survive using only one pill that contained the bacteria. Fortunately, some studies are already exploring this method, as well as using FMT for other cancers.
This article has been updated to note that researchers at the UPMC Hillman Cancer Center played a leading role in this study, including treating these patients.