An experimental treatment made from carefully screened donor stool allowed some adults with severe peanut allergy to tolerate more peanut before reacting, according to a small early-stage clinical trial.
Six of the 15 participants showed an increased reaction threshold several months after receiving capsules containing fecal microbes. The findings, published in Science Translational Medicine, offer early evidence that changing the gut microbiome could influence the immune system’s response to food. But the treatment did not eliminate participants’ allergies, and the study was far too small to show that the effects are permanent.
The phase 1 trial was primarily designed to evaluate the safety of oral fecal microbiota transplantation in people with peanut allergy. It had no placebo group, and both the participants and researchers knew that the treatment was being given. Those limitations make it impossible to determine how consistently the therapy works or how much of the apparent improvement was caused by the transplant.
Researchers enrolled young adults who reacted to very small amounts of peanut during medically supervised food challenges. In the first part of the study, 10 participants took 36 frozen capsules containing microbes collected from healthy donors without food allergies.
When the participants underwent another food challenge four months later, three could consume more peanut before developing symptoms.
Five additional participants took antibiotics before receiving the same type of transplant. Antibiotics were intended to clear space within the existing gut microbiome, potentially making it easier for the donor microbes to become established. Three of those five participants later tolerated more peanut than they had before treatment.
That difference may suggest that antibiotic pretreatment helped, but the groups were too small to support a firm conclusion. Three responders out of five can look like a high success rate, but it represents only three people. The two groups also were not part of a large randomized comparison designed to test whether antibiotics improved the treatment.
The participants who responded still had peanut allergies. They could consume a larger amount before reacting, but they were not shown to tolerate ordinary servings without risk.
Raising the reaction threshold could nevertheless be meaningful. People with severe allergies may react to small amounts transferred through shared equipment, improperly labeled foods or other accidental exposures. A treatment that reliably increased the amount required to trigger a reaction might eventually provide an added layer of protection.
This trial did not establish that level of protection. Researchers do not yet know how long the changes last, whether repeat treatment would be needed or whether the approach would work in a larger and more varied population.
“This landmark study was the first to demonstrate that a microbiome-based therapy may improve food allergy in people while also revealing how gut bacteria, their metabolites, and the immune system work together to influence treatment response,” said Rima Rachid, director of the Food Allergy Program and the Allergen Immunotherapy Program at Boston Children’s Hospital.
The researchers also investigated why some participants appeared to respond while others did not.
Responders had changes in bile acids, substances produced by the liver and modified by bacteria in the digestive tract. Although bile acids are best known for helping the body digest fat, the compounds created when gut bacteria process them can also communicate with the immune system.
Laboratory and mouse experiments suggested that the transplanted microbes produced bile acid patterns that encouraged regulatory immune cells. These cells help maintain oral tolerance, the process through which the immune system learns to accept foods rather than treat them as threats.
“Food allergy reflects a failure of oral tolerance, the process by which the gut immune system learns to accept food, and what this study shows is that the right bacteria can help restore that process, working through bile acid metabolites to promote the immune cells that enforce tolerance,” said Talal Chatila, director of translational immunology at Boston Children’s.
Those experiments provide a possible explanation for the human results, but they do not prove that bile acid changes caused the participants to tolerate more peanut. Some of the strongest evidence about how the microbes influenced immune cells came from animal and laboratory models rather than directly from people.
The research also does not mean that consumers should try to alter their microbiomes with probiotics, antibiotics or do-it-yourself fecal transplants. The study used material from screened donors that was processed and administered under medical and research supervision.
Fecal microbiota transplantation can transmit harmful organisms. The Food and Drug Administration has warned of serious and potentially life-threatening infections linked to investigational fecal microbiota products, including cases involving material from donors who had undergone screening.
Antibiotics also carry risks and can disrupt the gut microbiome in unpredictable ways. The five-person antibiotic group does not provide evidence that people with food allergies should take antibiotics before another treatment or attempt to change their gut bacteria on their own.
The study reported that adverse events among the enrolled participants were mild and resolved on their own. Larger trials will still be needed to identify less common risks and determine whether benefits outweigh those risks.
Current peanut allergy treatments can raise the amount a person can tolerate, but they generally require continued treatment and do not guarantee protection from severe reactions. The possibility that a one-time microbiome treatment could produce longer-lasting immune changes is one reason the new findings are attracting attention.
Researchers are now studying more purified and concentrated microbial capsules that can be stored in a home refrigerator and taken under medical supervision. Other research will examine whether microbiome treatment can be combined with peanut oral immunotherapy.
For now, fecal microbiota transplantation for peanut allergy remains experimental. People with peanut allergies should continue avoiding peanut as directed, carrying prescribed epinephrine and following their existing emergency plans.
The research was supported by the Translational Research Program at Boston Children’s Hospital, the Broad Institute of MIT and Harvard Children’s Collaborative Award, End Allergies Together, The Food Allergy Fund, philanthropic donations and the National Institutes of Health.