Fecal microbiota transplantation may improve immunotherapy-related colitis

  • Immunotherapy-related colitis is a potentially serious side effect of immunotherapy that can force patients to pause cancer treatment 
  • The majority of patients in this study saw improvements in colitis after receiving fecal microbiota transplantation (FMT)
  • Colitis symptoms improved within a median of 1.5 days after treatment 

Targeting the gut microbiome with fecal microbiota transplantation (FMT) may help cancer patients with immunotherapy-related colitis avoid the need for steroids and other immune-suppressing treatments, according to researchers at The University of Texas MD Anderson Cancer Center.

Findings from the Phase 1/2 trial, published in Cell Reports Medicine, showed that nearly 77% of the first 13 patients treated with FMT saw improvements, with symptoms subsiding in a median of just 1.5 days. Eight of the 10 patients who responded remained in remission during follow-up. 

“What stands out in these results is the quick onset of clinical improvement from an early introduction of microbiome therapy as well as the number of patients who were able to resume cancer treatment,” said principal investigator Yinghong Wang, M.D., Ph.D., professor of Gastroenterology & Hepatology. “These findings suggest FMT may have a role earlier in the course of immunotherapy-related colitis as a quick and effective treatment that could mitigate the exposure to immunosuppressive treatment as well as related complications.”

What is immunotherapy-related colitis? 
Immunotherapy works by unleashing the immune system to recognize and eliminate cancer, but the treatment also can cause the immune system to mistakenly attack healthy tissue in some patients. One potential side effect is immunotherapy-related colitis, which can cause severe diarrhea, abdominal pain and inflammation of the colon. In some cases, immunotherapy-related colitis can compel patients to pause cancer treatment. 

Currently, colitis typically is treated with steroids and biologic therapies. FMT takes a different approach by transferring healthy gut bacteria from a screened donor into a patient’s digestive system to help restore a healthier balance of bacteria in the gut. 

Why are researchers looking for alternatives to steroids? 
Steroids and other immune-suppressing therapies can control inflammation, but using these treatments for a long time can increase the risk of infections and other side effects. There also are concerns about how suppressing the immune system could affect the body’s ability to respond to cancer.

Developing treatments that reduce the need for steroids is an important goal in managing side effects from cancer immunotherapy while still allowing the immune system to do its job. 

What did this study reveal about the gut microbiome?
Researchers analyzed stool, blood and tissue samples collected before and after FMT to understand why some patients responded, and others did not.

Patients who responded showed increases in several types of bacteria associated with a healthier gut and decreases in bacteria linked to intestinal inflammation relative to those who did not respond to treatment. Researchers also found differences in immune markers between patients who did and did not respond.

These findings may help researchers better understand how the gut microbiome influences inflammation and responses to treatment.

Reported side effects related to FMT were mild and included temporary abdominal discomfort, nausea and low-grade fever. Researchers plan to continue comparing FMT directly with standard treatments in larger, randomized studies, including launching additional clinical trials of FMT in treating different cancers, such as colorectal cancer, pancreatic cancer and lymphoma.

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This research was supported by the Adopt-A-Scientist Grant and UT MD Anderson institutional funds. A full list of collaborating authors and disclosures can be found with the full paper in Cell Reports Medicine.

What stands out in these results is the quick onset of clinical improvement from an early introduction of microbiome therapy as well as the number of patients who were able to resume cancer treatment. These findings suggest FMT may have a role earlier in the course of immunotherapy-related colitis as a quick and effective treatment that could mitigate the exposure to immunosuppressive treatment as well as related complications.

Yinghong Wang, M.D., Ph.D.

Gastroenterology & Hepatology