How ‘good’ bacteria from fecal transplants reduce peanut allergy

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; 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. The landmark study is the first to demonstrate that a microbiome-based therapy may improve food allergies in people while also revealing how gut bacteria, their metabolites, and the immune system work together to influence treatment response.

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-threatening allergic reactions, sometimes in response to the treatments.

“People with food allergies want freedom from constant anxiety and extreme vigilance, which means not having to 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.”

Search for a food allergy 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” bacterial 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 bacterial strains from donors with healthy gut microbiomes into 10 young adults with severe peanut allergies who reacted to even traces of peanuts. When tested four months after a one-time treatment of 36 pills taken over a few hours, three participants improved: Two participants ingested two to four peanuts before reacting and one tolerated more than four peanuts with no reaction.

In the next round of the study, participants took antibiotics before the fecal transplant to see if the donor bacteria transferred more successfully when they didn’t have to compete with the participants’ own resident gut microbes. Three of these five participants had improved peanut tolerance and could eat more than four peanuts before reacting, suggesting that the antibiotics did increase the efficiency of the microbiome transfer.

Why changing the microbiome affects food allergies

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 against allergic reactions.

“Food allergy reflects a failure of oral tolerance, the process by which the gut immune system learns to accept food,” says Chatila. “This study shows that the right bacteria can help restore that process, working through bile acid metabolites to promote the immune cells that enforce tolerance. Knowing how the bacteria restore tolerance to food in allergic individuals allows us to optimize the therapy for more effective outcomes.”

As for why some participants responded to treatment and others didn’t, Rachid hypothesizes that some patients may need multiple treatments or they may need a different donor microbiome.

“Food allergies become more ingrained in adults and are harder to treat than in kids, potentially requiring more intensive interventions,” says Rachid. “There’s likely not just one mechanism behind this condition, which will probably require precision medicine to treat everyone properly.”

Larger studies of fecal transplantation are needed 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. To that end, Rachid is leading a new study, in collaboration with the University of Minnesota, in which teens will receive microbe transplantation therapy. This newer therapy uses a purified, concentrated form of microbes that can be stored in a home refrigerator. Patients will take the capsules at home under medical supervision and will then undergo food challenges to evaluate for changes in their tolerance to peanuts. Rachid is also leading a third study that evaluates the newer concentrated formulation in combination with peanut oral immunotherapy.

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