Fecal Transplant Sustains Peanut Allergy Protection to 12 Months

RORγt+ regulatory T (Treg) cell expansion following fecal microbiota transplantation (FMT) persisted for up to 12 months in responders with severe peanut allergy, an effect linked to bacterial bile acid metabolism.

HCPLive previously reported the trial's overall response rates, including the antibiotic pretreatment signal identified in the study.² Antibiotic pretreatment before oral FMT raised the peanut allergy response rate to 60% from 30% without pretreatment. The phase 1 open-label trial enrolled 15 adults with peanut allergy, dosed with 36 capsules of oral encapsulated FMT from 1 of 3 screened donors.¹

The mechanistic data described here address why the effect endures after a single FMT dose. Prior work from the Chatila lab established RORγt+ Treg cells as necessary for anaphylaxis protection in mouse models of food allergy.¹

"One of the things we didn't know is: if FMT were to work, when will we see the response?” said Rima Rachid, MD, director of the Food Allergy Program and the Allergen Immunotherapy Program, Boston Children's Hospital, in an interview with HCPLive. "We saw a response at 1 month, and it persisted at 4 months post-FMT, and that was very promising because this was a proof-of-concept study."

Durable RORγt+ Treg Cell Expansion After FMT

RORγt+ Treg cells increased significantly in responders at 1 month (P =.0480) and 4 months (P =.0052) after FMT and remained elevated at 12 months (P =.0004) among the subset completing the optional exit visit. Nonresponders showed no significant Treg change at any timepoint.¹

Circulating IL-13+ CD4 T cells, a marker of TH2 activity, decreased in responders at 1 month (P =.0286). This reduction was not sustained at later timepoints, and investigators noted it may reflect the small sample size rather than a true loss of effect.¹

RORγt+ Treg cells were previously identified as necessary for anaphylaxis protection in the Il4raF709 mouse model of food allergy, with deletion of Rorc in Tregs eliminating protection. Patients with food allergies have shown decreased RORγt+ Treg frequency compared with healthy controls at baseline.¹

Bile Acid Metabolism and Bacteroides Link to Protection

Standard 16S and shotgun metagenomic sequencing of human stool did not distinguish responders from nonresponders. Rachid attributed this to the small cohort or to a localized effect below the level of detection in stool.

“The interesting part came when we actually took the stools of the patient who responded 4 months post-transplantation, and we put them into an allergy-prone mouse model that anaphylaxes upon exposure to food,” Rachid said. “What happened was that while the stools of these patients who responded as baseline did not protect from anaphylaxis. The stools of the patient, when they were collected 4 months post fecal transplantation, protected the mice from anaphylaxis, and that wasn't the case when we took the stools of the patients who didn't respond. So that became very interesting.”

Metagenomic analysis of the protected mice identified roughly 10 differentially abundant bacterial taxa, most notably a nearly 1000-fold increase in Bacteroidales species. Untargeted metabolomics showed elevated bile acids in human responders and elevated bile acid metabolites in protected mice. Bacteroides ovatus, a species expressing bile salt hydrolase (BSH), was enriched in the responder-derived mice.¹

"We used the wild bacteria, and it completely protected from anaphylaxis," said Rachid. "But when we used the bacteria that did not have the capacity to hydrolyze the bile acids, there was no protection, and that's why we think this protection is mediated, at least partly, via the metabolism of bile acids."

Rachid said her team is now developing a purified, refrigerator-stable microbial formulation and a combination study with peanut oral immunotherapy, building on these mechanistic findings.¹

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(eaee3263). doi:10.1126/scitranslmed.aee3263

2. Antibiotic Pretreatment Improves FMT Response in Peanut Allergy. HCPLive. hcplive.com/view/antibiotic-pretreatment-fmt-peanut-allergy-phase-1-trial. Published August 12, 2026. Accessed August 12, 2026.