MD Anderson Clinical Trial Shows Fecal Microbiota Transplants May Be Useful for Fighting Cancer
Additional research may lead to precision medicine FMT treatments for patients with specific cancers
Research continues to show that the human gut microbiome plays a significant role in a person’s health and longevity. One recent example is a clinical trial study conducted by scientists at MD Anderson Cancer Center in Houston which demonstrated that fecal microbiota transplants (FMTs) can help in the eradication of some cancers.
If approved for clinical treatment of cancer, the use of FMT may increase the demand for diagnostic tests to verify that the approach worked in a patient.
Our guts are home to trillions of microorganisms (aka, microbiota), known as the gut microbiome, which serve many important functions in the body. The microbiome is a delicate ecosystem that can be pushed out of balance when unfavorable microbes outnumber advantageous ones.
An FMT is an uncomplicated and powerful method of repopulating the microbiome with beneficial microbes. The researchers at MD Anderson administered FMTs from donors with advanced cancers that had been completely cured by immunotherapy into the guts of patients whose cancers were not improving.
“[Early reports] demonstrate that gut microbiota is contributing to immunotherapy resistance in at least some patients and provide hope that by changing the microbiome, some will respond,” Jonathan Jacobs, MD, PhD, a gastroenterologist at the Fielding School of Public Health at the University of California, Los Angeles (UCLA), told NBC News. Jacobs was not involved in the MD Anderson research.
“These early reports of patients who were previously immunotherapy-resistant but experienced clinical response after receiving FMT [fecal transplants] and immunotherapy retreatment are very exciting,” said Jonathan Jacobs, MD, PhD (above), a gastroenterologist at the Fielding School of Public Health at the University of California, Los Angeles, in an interview with NBC News. (Photo copyright: UCLA.)
‘Miraculous’ Treatment for Cancer
Fecal microbiota transplant is a procedure where stool from a healthy donor is transplanted into the microbiome of a patient plagued by a certain medical condition. The procedure has been used as a standard treatment for recurrent Clostridioides difficile for years and is currently being studied as a potential cure for illnesses such as Parkinson’s disease, autism, obesity, and inflammatory bowel disease.
The premise of the MD Anderson clinical trial study was that gut bacteria from the now cancer-free individuals may assist the immune systems of the current patients to recognize and fight their cancers. The scientists focused their efforts on PD-1 immune checkpoint inhibitors that help keep white blood cell lymphocytes (T cells) from attacking other cells in the body.
PD-1 inhibitors are especially effective in treating tumors known as microsatellite instability-high cancer tumors. This type of tumor has an unusually large numbers of DNA mutations. PD-1 inhibitors help pinpoint these mutations and attack the cancerous tumors.
“They’re miraculous drugs,” Timothy Yeatman, MD, PhD, associate director of translational research at the Tampa General Hospital Cancer Institute, told NBC News. “They’ve been able to cure people with no chemotherapy, no radiotherapy, or no surgery.”
Yeatman also said that some patients “experience improvements that are barely believable: people with mere months to live who are then cured of their disease. In medical parlance, this is referred to as a complete response.”
FMT Treatment Brings Fast Results
Yinghong Wang, MD, PhD, a gastroenterology specialist and professor in the department of gastroenterology, hepatology and nutrition at MD Anderson, said in a news release that positive results for cancer patients undergoing the FMT treatment can appear expeditiously.
“The quickest response can be seen within 24 hours. Patients have reported having much better energy and appetite the next day. Some say they feel like a new person,” she said. “Usually, though, I’d recommend giving it at least a week. If two weeks pass by without any discernable benefit, it probably wasn’t effective.”
According to Wang, FMTs can be delivered by several methods that fall into two categories:
- Lower GI tract: The colonoscopy method is used very frequently since it allows more thorough coverage of the colon’s interior walls and reduces the chance of leakage after the procedure. However, liquid donor stool can also be delivered via enema.
- Upper GI tract: These include frozen or freeze-dried capsules that can be swallowed, as well as liquids that can be placed directly in the GI tract via a feeding tube or upper endoscopy procedure.
This ongoing pilot study at MD Anderson could aid in the advancement of using the gut microbiome to help the immune system fight all sorts of diseases.
Future Developments of FMT Research
MD Anderson has partnered with biotechnology startup Kanvas Biosciences, which developed a technology known as HiPR-FISH (high-phylogenetic-resolution microbiome mapping by fluorescence in situ hybridization) to examine the relationships between gut bacteria and the immune system. This tool enables scientists to identify key microbial strains and place those strains in a pill that MD Anderson will use in further research to determine if PD-1 inhibitors can help the immune system on a larger scale.
“We have essentially made a synthetic version of the superdonor stool and then optimized and immortalized it so that it can be reproduced and used in the treatment of cancer patients worldwide,” Matthew Cheng, MD, a trained medical microbiologist and co-founder and CEO of Kanvas, told NBC News.
More research and clinical trials are needed before fecal microbiota transplants can be used on a mainstream basis in the treatment of cancer. However, the MD Anderson research is promising in foreseeing the possibility that cancer patients who do not respond well to immunotherapy may have better luck through a personalized medicine approach geared to specific patients.
As such, the research is of interest to pathologists who want to learn more about the potential role of the human microbiome in precision medicine and clinical laboratory testing.
“It’s possible that even better outcomes could be obtained with a more precise understanding of the recipient’s microbiome, genetics, type of cancer, and antitumor immune responses, to select the optimal combinations,” said Jacobs in the NBC News interview.
—JP Schlingman
