What is already known
Cancer immunotherapy has shown promise for treating a variety of cancers, but it also predisposes patients to gut inflammation. Transferring gut microbes from people with cancer to mice results in increased responses to immunotherapy, but whether microbiota transplant could also help to alleviate the intestinal side effects of the therapy remains unclear.
What this research adds
Researchers examined 12 cancer patients receiving immunotherapy who had severe gut inflammation or diarrhea and who underwent fecal microbiota transplant (FMT). Most of the study participants showed improvement in their intestinal symptoms. FMT increased the diversity of the gut microbiota and suppressed the activity of inflammatory immune cells, the researchers found.
Conclusions
The findings suggest that FMT is an effective strategy to mitigate the intestinal side effects of cancer immunotherapy.
Cancer immunotherapy has shown promise for treating a variety of cancers, but it also predisposes patients to gut inflammation. A small clinical study now shows that fecal microbiota transplant (FMT) can alleviate gut inflammation and diarrhea in cancer patients receiving immunotherapy.
The findings, published in Science Translational Medicine, suggest that FMT is an effective strategy to mitigate the intestinal side effects of cancer immunotherapy.
Cancer immunotherapy unleashes the immune system against tumor cells. This can improve outcomes in people with advanced cancers, but it also causes various immune-related side effects such as colitis — a condition characterized by inflammation of the inner lining of the colon.
While transferring gut microbes from people with cancer to mice is known to result in increased responses to cancer immunotherapy, whether FMT could also help to alleviate the intestinal side effects of the therapy remains unclear.
To address this question, Taylor Halsey at the University of Texas MD Anderson Cancer Center in Houston and her colleagues examined 12 cancer patients receiving immunotherapy who had severe gut inflammation or diarrhea and who underwent FMT.
Improving symptoms
FMT was given an average of 89 days after the onset of intestinal symptoms. Of the 12 study participants, 10 showed improvement in symptoms and seven showed complete responses. Three patients received additional FMT for partial responses, and four required additional immunosuppressant treatment.
At 7 and 30 days after FMT, no complications were reported. This suggests that the treatment is generally safe and well tolerated.
Next, the researchers compared the participants’ microbiota compositions before FMT. At baseline, Bifidobacterium and Collinsella bacteria were found at lower levels in people who showed a complete response to the treatment compared with those who didn’t.
Reducing inflammation
The researchers also identified microbes that were present at different levels in the guts of participants after receiving FMT. Bacteria including Collinsella, Bifidobacterium and Coprococcus were enriched in people who showed a complete response to FMT, whereas Tyzerella bacteria were reduced.
Finally, the team found that a type of inflammatory immune cells called CD8+ T cells were decreased in people who showed a complete response to FMT but not in those who didn’t.
Larger clinical studies are needed to better characterize the efficacy and safety of FMT as a strategy to alleviate immunotherapy-related intestinal side effects, the researchers say. However, they add, “we expect that FMT will become a useful approach to treat patients with [immune-mediated colitis] at earlier stages of presentation.”
