Fecal transplant shows ‘very encouraging’ results for treatment of peanut allergy
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PHOENIX — A fecal microbiota transplant from healthy donors enabled patients with severe peanut allergy to safely eat small amounts of peanut, according to a presentation at American Academy of Allergy, Asthma & Immunology Annual Meeting.
“These results were 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 fecal microbiota transplant (FMT) led to a significant increase in the threshold of reactivity to peanut at both 1 month and 4 months after treatment, showing that the effect was prolonged. This study is offering hope that microbiome interventions may be effective in food allergy.”
Rationale for use of FMT
Accumulating evidence suggests that the gut microbiota plays a major role in the development of food allergy, Rachid said during her presentation at AAAAI Annual Meeting.
Based on preclinical studies that Rachid and colleagues conducted that showed bacteriotherapy can treat and prevent food allergy in mice, the researchers then sought to evaluate whether microbiota of healthy controls would protect against food allergy in mice. They took stool samples from healthy and food-allergic babies and injected them into food-allergic mice and discovered that the fecal transplant from healthy babies protected the mice from anaphylaxis and conferred significant drops in IgE and mast cell protease levels, whereas transplant from food-allergic babies or no transplant at all did not lead to any protection.
Rachid also acknowledged that FMT is used as standard of care for the treatment of Clostridium difficile infection, with a cure rate of up to 96%. Originally FMT had been administered via colonoscopy, nasogastric (NG) tube or enema, but recently data have shown that administration of FMT in frozen encapsulated matter conferred a similar cure rate as colonoscopy for C. difficile.
“That became very attractive to us as we were not comfortable putting NG tubes or doing a colonoscopy to evaluate the safety of FMT in food-allergic patients,” Rachid said. “But, once these capsules became available, we decided that we were going to proceed with a trial.”
Early data
Rachid presented results from that trial, an open-label phase 1 trial to evaluate the safety and efficacy of FMT among 15 participants aged 19 to 34 years (median age, 22 years; women, n = 8; white, n = 13) who reacted to 100 mg of peanut protein or less, which is equivalent to less than half a peanut. At baseline patients had a median skin prick test result of 13 mm (range, 6-20) and median peanut IgE was 22.9 kU/L (range, 0.28-309).
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 the donor passes a second round of serological and stool tests.
“There is one caveat about using FMT for food allergy, in that it may potentially cause an allergic reaction in patients with severe food allergies if the donor ingested the food allergens that the recipient is allergic to,” Rachid said.
“To bypass that, we met with the donors at OpenBiome and trained them in avoiding peanuts and tree nuts, even in traces, for 1 week prior to stool donation,” she said, adding that the samples also were tested using mass spectrometry and liquid chromatography for traces of peanut and tree nut.
In part A of the trial, 10 patients received 36 capsules of FMT slowly and incrementally 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 clearing out their own gut microbiome ahead of receiving the donor bacteria, and then received FMT after a 2-day hiatus in the same fashion over 3 hours.
Overall, three patients (30%) in part A and three (60%) in part B tolerated larger amounts of peanut at 1 and 4 months after FMT treatment.
In part A, one patient who reacted to 100 mg of peanut protein at study entry reacted to 300 mg, or more than one peanut, at 1 month and 4 months; one patient who reacted to 10 mg peanut protein at study entry reacted to 300 mg at 1 month and to 600 mg, or more than two peanuts, at 4 months; and the third patient reacted to 100 mg at entry and tolerated all doses at 1 and 4 months (cumulative more than 1,000 mg, or four peanuts).
In part B, two patients who reacted to 100 mg at study entry reacted to 600 mg at 4 months, after having to forgo the 1-month oral food challenge due to the COVID-19 lockdown, and a third patient who only tolerated 30 mg at entry reacted to 600 mg at both 1 month and 4 months following FMT.
“In comparison, it takes 6 months of oral immunotherapy to reach that level of peanut tolerance, and we know OIT is more challenging in adults,” Rachid said. “The efficacy effect was prolonged and persisted for at least 4 months following FMT.”
Researchers reported no serious adverse events and no allergic reactions related to FMT in either part of the trial. Four patients in part A experienced mild adverse events that resolved within 2 days, including fatigue, stomach pain, headache and nausea. One patient in part B experienced mild diarrhea.
Mechanistic studies of the 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, along with reductions in IL-13-positive, CD4-positive T-helper cells, which are associated with allergy.
“These regulatory T cells are very important for tolerance; if you delete ROR-gamma expression from regulatory T cells in mice, these mice can develop anaphylaxis despite using the right protective bacterial therapy,” Rachid said.
Moreover, allergy-prone mice transplanted using stools collected from the responders 4 months following FMT showed similar immune changes and showed protection from anaphylaxis when challenged with allergens.
Researchers next plan to conduct a phase 2 trial of patients with antibiotic pretreatment and a purified Microbial Transplantation Therapy, or MTT, preparation in collaboration with Alexander Khoruts, MD, from University of Minnesota. MTT can be administered at home and stored in the refrigerator, which Rachid described as a “realistic approach for the future” use of FMT.
References:
- Abdel-Gadir A, et al. Nat Med. 2019;doi:10.1038/s41591-019-0461-z.
- Good early results with fecal microbiota therapy for peanut-allergic patients. https://www.eurekalert.org/news-releases/944014. Published Feb. 26, 2022. Accessed Feb. 26, 2022.