Fecal transplant shows ‘very encouraging’ results for treatment of peanut allergy

February 26, 2022

4 minute read

Source/Disclosures

Source:

Interventions by Rachid R. Microbiome in food allergy. Presented at: AAAAI Annual Meeting; February 25-28, 2022; Phoenix (hybrid meeting).

Disclosures:
Rachid reports a stake in Pareto Bio and research grants from Aimmune Therapeutics, Food Allergy Fund, Food Allergy Research and Education, and Siolta Therapeutics.


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PHOENIX – A transplant of fecal microbiota from healthy donors has enabled patients with severe peanut allergy to safely eat small amounts of peanuts, according to a presentation at the annual meeting of the American Academy of Allergy , Asthma & Immunology.

“These results are very encouraging” Rima Rachid, MD, director of the allergen immunotherapy program and co-director of the food allergy program at Boston Children’s Hospital, said in a press release. “A single faecal microbiota transplant (FMT) resulted in a significant increase in peanut responsiveness threshold both 1 month and 4 months after treatment, showing that the effect was prolonged. This study offers hope that microbiome interventions may be effective in food allergies.

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Rationale for using FMT

Accumulating evidence suggests that the gut microbiota plays a major role in the development of food allergy, Rachid said during his presentation at the AAAAI Annual Meeting.

Rima Rachid, MD

Rima Rachid

Based on preclinical studies conducted by Rachid and colleagues that showed that bacteriotherapy can treat and prevent food allergy in mice, the researchers next sought to assess whether the microbiota of healthy controls would protect against food allergy in mice. the mouse. They took stool samples from healthy, food-allergic babies and injected them into food-allergic mice and found that the fecal transplant from healthy babies protected the mice from anaphylaxis and conferred significant drops in IgE and mast cell protease levels, while food-allergic babies or no transplant at all provided no protection.

Rachid also acknowledged that FMT is used as the standard of care for the treatment of Clostridium difficile infection, with a cure rate of up to 96%. Originally, FMT was administered by colonoscopy, nasogastric (NG) tube, or enema, but recent data has shown that administration of FMT in frozen encapsulated material confers a cure rate similar to that of colonoscopy for It’s hard.

“It became very appealing to us because we weren’t comfortable putting in NG tubes or doing colonoscopy to assess the safety of FMT in food-allergic patients,” Rachid said. “But, once these capsules became available, we decided we would give it a try.”

First data

Rachid presented the results of this trial, an open-label phase 1 trial to assess the safety and efficacy of FMT in 15 participants aged 19-34 years (median age, 22 years; females, n=8 ; whites, n = 13) who responded to 100 mg of peanut protein or less, which equals less than half a peanut. At baseline, patients had a median skin test result of 13 mm (range, 6-20) and median peanut IgE was 22.9 kU/L (range, 0.28-309).

The researchers used donor stool from the nonprofit OpenBiome Stool Bank, which uses careful donor screening and blood and stool testing, as well as a 60-day quarantine for stool samples until that the donor passes a second series of serological and stool tests.

“There is a caveat to the use of FMT for food allergies, in that it can potentially cause an allergic reaction in patients with severe food allergies if the donor has ingested the food allergens to which the recipient is allergic,” Rachid said.

“To circumvent this, we met with OpenBiome donors and trained them to avoid peanuts and tree nuts, even in trace amounts, for 1 week prior to stool donation,” she said, adding that the samples had also been tested by mass and liquid spectrometry. chromatography for traces of peanuts and nuts.

In Part A of the trial, 10 patients received 36 capsules of FMT slowly and gradually over 3 hours. In part B of the trial, five of the patients received 4 days of pretreatment with broad-spectrum antibiotics as a means of eliminating their own gut microbiome before receiving the donor bacteria, then received FMT after a break in 2 days in the same mode over 3 hours.

Overall, three patients (30%) in Part A and three (60%) in Part B tolerated greater amounts of peanuts 1 and 4 months after FMT treatment.

In Part A, a patient who responded to 100 mg of peanut protein at study entry responded to 300 mg or more of a peanut at 1 month and 4 months; one patient who responded to 10 mg of peanut protein at study entry responded to 300 mg at 1 month and to 600 mg, or more than two peanuts, at 4 months; and the third patient responded to 100 mg at entry and tolerated all doses at 1 and 4 months (cumulative greater than 1000 mg, or four peanuts).

In Part B, two patients who responded to 100 mg at study entry responded to 600 mg at 4 months, after having to forgo the one-month oral food challenge due to the COVID-19 lockdown. 19, and a third patient who tolerated only 30 mg at entry responded to 600 mg both 1 month and 4 months after FMT.

“In comparison, it takes 6 months of oral immunotherapy to reach this level of peanut tolerance, and we know that OIT is more difficult in adults,” Rachid said. “The efficacy effect was prolonged and persisted for at least 4 months after FMT.”

The researchers reported no serious adverse events and no allergic reactions related to FMT in either part of the trial. Four patients in Part A had mild adverse events that resolved within 2 days, including fatigue, stomach pain, headache, and nausea. One patient in Part B presented with mild diarrhea.

Mechanistic studies of participants’ blood samples showed that those who responded to FMT treatment had increases in ROR-gamma t-positive regulatory T cells, which are associated with immune tolerance, as well as reductions in IL- 13-positive, CD4-positive. -helper cells, which are associated with allergy.

“These regulatory T cells are very important for tolerance; if you suppress ROR-gamma expression of regulatory T cells in mice, those mice can develop anaphylaxis despite using the right protective bacterial therapy,” Rachid said.

Additionally, allergy-prone mice transplanted using feces collected from responders 4 months after FMT showed similar immune changes and showed protection against anaphylaxis when challenged with allergens. .

The researchers then plan to conduct a phase 2 trial in patients with antibiotic pretreatment and a purified microbial transplantation therapy preparation, or MTT, in collaboration with Alexandre Khoruts, MD, from the University of Minnesota. MTT can be administered at home and stored in the refrigerator, which Rachid described as a “realistic approach for future use” of FMT.

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