Fecal Microbiota Transplant Boosts Peanut Tolerance in Phase 1 Trial

A single dose of oral encapsulated fecal microbiota transplantation (FMT) increased the peanut reactivity threshold in 6 of 15 adults with peanut allergy (40%) in a phase 1 open-label trial, with the effect sustained at 4 months and, in a subset, out to 12 months.¹

“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, MD, director of the Food Allergy Program and the Allergen Immunotherapy Program, at Boston Children’s Hospital, in a statement.²

Peanut oral immunotherapy with AR101 (Palforzia) was the only FDA-approved disease-modifying option for peanut allergy, but the manufacturer discontinued the product, leaving no approved peanut oral immunotherapy (OIT) on the market.³ Off-label desensitization protocols still require close to 6 months of daily dosing to reach a 300 mg tolerance threshold and carry high rates of allergic reactions, taste aversion, and nonadherence.¹ Prior mouse work from this group showed FMT from healthy donors, but not from patients with food allergy, protects against anaphylaxis in a food allergy–prone model, motivating this first-in-human application of FMT to peanut allergy.⁴

Peanut Reactivity Threshold Outcomes in the FMT Trial

Investigators enrolled 15 adults aged 18 to 40 years, all reactive to ≤ 100 mg of peanut protein on double-blind placebo-controlled food challenge (DBPCFC) at baseline.¹ In part A, 10 participants received a single dose of 36 encapsulated FMT capsules from 1 of 3 nonatopic donors without antibiotic pretreatment, and 3 of 10 (30%; 95% CI, 6.7-65.3%) achieved secondary efficacy, defined as an increased reactivity threshold to 300 mg or 600 mg of peanut at 1 and 4 months.

In part B, 5 additional participants received FMT after a 4-day pretreatment regimen of oral vancomycin, neomycin, and metronidazole, and 3 of 5 (60%; 95% CI, 14.7-94.7%) achieved secondary efficacy. FMT was safe across all 15 participants, with only 3 grade 1 and 2 grade 2 adverse events, all resolving within 12 to 48 hours and nonconsistent with immediate hypersensitivity. Five of 6 responders were male compared with 2 of 9 nonresponders (P =.041), though the cohort was too small to draw firm conclusions on sex as a predictor.

Microbiome Mechanism and Bile Acid Metabolism in Responders

Responders showed no change in total circulating Treg cell percentages but had significant increases in tolerogenic RORγt+ Treg cells at 1 month (P =.0480) and 4 months (P =.0052) after FMT, sustained at 1 year (P =.0004) among those completing the exit visit. Responders also had a decrease in circulating IL-13-expressing CD4 T cells at 1 month (P =.0286).

Human stool 16S and metagenomic profiles did not distinguish responders from nonresponders. Transfer of post-FMT responder stool into germ-free Il4raF709 mice protected against anaphylaxis across 3 sensitization models, while nonresponder stool did not. Protection tracked with Bacteroides colonization, gut RORγt+ Treg cell expansion, and suppression of IL-13+ TFH13 cells and intestinal mast cell expansion.

Serum cholate rose in responders after FMT but not in nonresponders. Deleting the bile salt hydrolase gene from Bacteroides ovatus eliminated both its protective effect against anaphylaxis and its ability to induce RORγt+ Treg cells in mice, implicating microbial bile acid metabolism as a driver of oral tolerance.

Investigators note the dose and frequency of FMT remain unoptimized, and the role of antibiotic pretreatment in maximizing response requires further study in larger, randomized, double-blind, placebo-controlled trials involving both sexes.¹

“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,” Rachid said.

References

1. Rachid R, Martinez-Blanco M, Kuziel GA, et al. Fecal microbiome transplant in food allergy in humans and mice identifies a role for bile acid metabolites in oral tolerance. Sci Transl Med. 2026;18(eaae3263). doi:10.1126/scitranslmed.aee3263

2. How ‘good’ bacteria from fecal transplants reduce peanut allergy. EurekAlert! Published August 5, 2026. Accessed August 5, 2026. https://www.eurekalert.org/news-releases/1138079?

3. Wood and Ross. Palforzia Discontinued, Ending the Only FDA-Approved Peanut OIT Option. HCPLive. Published July 31, 2026. Accessed August 5, 2026. https://www.hcplive.com/view/palforzia-discontinued-ending-only-fda-approved-peanut-oit

4. ClinicalTrials.gov. Fecal microbiota transplantation for food allergy. NCT02960074. https://clinicaltrials.gov/study/NCT02960074