Some 33 million Americans have severe food allergies. Now, researchers at Boston Children's Hospital may have found a promising solution. In a small clinical trial, Rima Rachid, MD , director of the Food Allergy Program and the Allergen Immunotherapy Program, and Talal Chatila, MD, director of translational immunology, and their colleagues found that some participants with peanut allergies experienced a higher tolerance to peanuts months after receiving a fecal transplant from a healthy donor without food allergies. Their findings are published today in Science Translational Medicine.
"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," says Rachid. "Larger studies of fecal and microbiota transplantation are now essential to confirm these findings, identify the patients most likely to benefit, and discover beneficial bacteria that could be developed into targeted probiotic therapies for food allergy."
Of the most common food allergy triggers, peanut and tree nuts cause the most severe, life-threatening allergic reactions. Certain antibody medications or small dose exposure immunotherapy can raise tolerance to a sensitive food, but allergic reactions soon return once the therapy stops. Even if taken as prescribed, patients still may experience life-threating allergic reactions, sometimes in response to the treatments.
"People with food allergies want freedom from constant anxiety and extreme vigilance and to not have be on guard for potentially dangerous exposures every time they leave the house," says Rachid. "Patients don't want therapies that have to be taken indefinitely and instead are looking for a permanent disease modification or cure."
In earlier work, Chatila and Rachid's team learned that when researchers transferred stool samples from babies with food allergies into allergy-prone mice, the mice went into anaphylaxis. Alternatively, mice that received fecal samples from healthy babies were protected from allergic reactions . In that study, the team identified a handful of "good" bacteria strains found in healthy babies' guts that protect against allergic reactions .
For the newest trial, Rachid and her team used frozen "poop pills" to transfer these good bacteria strains from donors with healthy gut microbiomes into 10 young adults with severe peanut allergies who reacted to traces of peanuts. After a one-time treatment of 36 pills taken each over few hours, three participants improved when tested four months later tolerating eating multiple peanuts. In the next round of the study, participants took antibiotics before the fecal transplant to see if the donor bacteria transferred more successfully when it didn't have to compete with the participants' own resident gut microbes. Three of these five participants improved in peanut tolerance and ingested more than four peanuts before reacting, suggesting that the antibiotics did increase the efficiency of the microbiome transfer.
Next, the investigators explored how the fecal transplants reduced food allergies. When the team analyzed blood samples from the research participants, those who responded to the therapy had increased levels of bile salts compared to the people who didn't respond. Bile salts are made in the liver, stored in the gallbladder, and released into the small intestine to break down fats to better absorb them. The good bacteria from the fecal transplants seemed to be more adept at metabolizing bile salts than the original bacteria in the allergic participants. In additional experiments, the team found that by metabolizing bile salts the good bacteria increased levels of immune regulatory cells that protect from allergic reactions.
"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," says Chatila. "Knowing how the bacteria restore tolerance to food in allergic individuals allows us to optimize the therapy for more effective outcomes."
Rachid is now leading a new study in which teens will receive microbe transplantation therapy in collaboration with Alexander Khoruts, MD, of the University of Minnesota. This newer therapy uses a purified concentrated form of microbes than the poop pills that can be stored in a home refrigerator. Patients will take the capsules from home under medical supervision and will then undergo food challenges to evaluate for changes in their tolerance to peanut. Rachid leads a third study that evaluates the effect of the combination of the newer concentrated formulation along with peanut oral immunotherapy.
Other researchers on the study included Eric Alm, PhD, and Matthieu Groussin, PhD, of the Massachusetts Institute of Technology; Elizabeth Hohmann, MD, of Massachusetts General Hospital; Seth Rakoff-Nahoum, MD, PhD, of Boston Children's Hospital and Gavin Kuziel, PhD, from his lab; Curtis Huttenhower, PhD, of the Harvard School of Public Health; Monica Martinez-Blanco, PhD, and Emmanuel Stephen Victor, PhD, of the Chatila lab.
The studies were funded by grants from the Translational Research Program at Boston Children's, the Broad Institute of Massachusetts Institute of Technology and Harvard Children's Collaborative award, End Allergies Together organization, The Food Allergy Fund organization, philanthropic donations, and the National Institutes of Health.
