Rima Rachid, MD, from Boston Children’s Hospital.

Rima Rachid, MD

 remains difficult to manage, with no approved therapy offering durable disease modification once treatment stops. Earlier work identified dysbiosis in the gut microbiome of food-allergic infants, along with specific Clostridiales and Bacteroidales bacteria capable of protecting against anaphylaxis in mouse models.¹ These findings drove the design of clinical trials evaluating fecal microbiota transplantation (FMT) as a treatment for peanut allergy.

A phase 1 trial of oral FMT showed durable effects, with RORγt+ regulatory T cell expansion persisting up to 12 months in responders, an effect linked to bacterial bile acid metabolism and Bacteroides ovatus colonization.² Antibiotic pretreatment before FMT also raised the response rate from 30% to 60% in this cohort.²

A second-generation, purified formulation known as microbiota transplantation therapy (MTT) was developed in collaboration with the microbiota therapeutic programs at the University of Minnesota. MTT is > 99% microorganism by content, requires only 5 capsules compared with 36 in the original protocol,² and remains stable at standard refrigerator temperature for approximately 6 months. A phase 2 trial is now randomizing 24 patients to antibiotic pretreatment or placebo before MTT dosing, with reactivity assessed through food challenges at 1 and 4 months.³

Rima Rachid, MD, co-director of the Food Allergy Program at Boston Children's Hospital and associate professor of pediatrics at Harvard Medical School, is leading this research. In the following Q&A, Rachid discusses the new MTT formulation, the design of the ongoing phase 2 trial, and the mechanistic findings shaping future donor selection strategies.

Q&A: Microbiota Transplantation Therapy Simplifies Dosing for Peanut Allergy

: Can you walk through the new peanut allergy study and the MTT formulation developed with the University of Minnesota?

 This is in collaboration with Alex Khoruts from the microbiota therapeutic programs. He is the director of the microbiota therapeutic programs at the University of Minnesota. Alex and his team have developed a second-generation fecal transplantation formulation where the fecal material is highly purified, so you end up with what we call microbiota transplantation therapy, or MTT. It is highly concentrated in microorganisms and contains less than 1% fecal non-microorganism material, so 99% of it is microorganisms coming from a human gut.

In the first study, the proof-of-concept phase 1, we… [used capsules] kept at minus 80 degrees in a research freezer, and when the patient comes, you have to administer it within 90 minutes of thawing.

MTT [is] also encapsulated, double encapsulated, [and] there [are] absolutely no complaints about taste or smell. It can also stay at 4 degrees Celsius, the temperature of a home fridge, for about 6 months [and remain] stable.

MTT cuts dosing from 36 capsules to 5 and is refrigerator-stable for about 6 months, replacing the -80°C storage the original FMT protocol required.

A phase 2 trial is randomizing 24 patients to antibiotic pretreatment or placebo before MTT dosing, with food challenges at 1 and 4 months.

A 1000-fold rise in Bacteroidales abundance was linked to transplant efficacy, a signal that may guide future donor selection.

How does the capsule dose and storage of MTT compare with the original fecal microbiota transplant protocol?

 The dose required is 5 capsules, as opposed to 36 capsules in the first trial. You are able now to [administer] to younger patients because it's a very small dose, relatively speaking.

What is the design of the current phase 2 peanut allergy clinical trial using MTT?

 We're no longer just administering FMT under medical supervision. We're bringing the patient in after they react to a trace of peanut, then randomizing them to receive either antibiotics or placebo. Those who receive antibiotics come in and receive MTT: 5 capsules under medical supervision, followed by another 5 capsules the next day, and then 2 capsules daily for a total of 28 days.

Then, they’ll undergo a food challenge at 1 month and 4 months post-MTT. Those on placebo receive placebo capsules. This study will enroll 24 patients, [with] 1-to-1 randomization, so 12 will get MTT and 12 will get placebo. We are very close to closing enrollment.

What are the next steps for larger MTT trials and the powder formulation for younger patients?

: What we're hoping for is to do larger studies. We will need larger studies to evaluate the donor-patient effect and see if particular patients might respond better to particular donors. We are aiming for 50, hopefully 100, patients… [who will receive] MTT from different donors… and hope to administer it for a period of at least 6 months to see the effect.

Another good news about MTT is that there is now a powder formulation that is in progress, and that powder formulation could potentially be evaluated in patients who cannot swallow capsules, so we’re talking about younger patients. There is a lot of evidence in food allergy that the sooner you intervene, the better, so we're hoping to take it down to ages 4 to 11 years and see the effect of this powder formulation.

What role do Bacteroidales and Clostridiales gut bacteria play in protecting against food allergy and anaphylaxis?

 What I think is very interesting is the Bacteroidales part. We saw the same type of bacteria that protects from anaphylaxis in a study where, initially, in the Nature Medicine paper we published back in 2019, we enrolled 156 babies. There were 54 who were food allergic, and the rest were controls.

We continued following them every few months up until 13 months of age, and when we analyzed the microbiome, we found there was continuous dysbiosis, an abnormal microbiome, in patients who were food allergic. But there [were] some carefully selected bacteria, Clostridiales species, and separately a few Bacteroidales species. This was in collaboration with our colleagues at Brigham, Lynn Bry and Georg Gerber.

We took those bacteria [and] put them into a highly allergic mouse model, and there was complete protection from anaphylaxis. That experiment was repeated multiple times. There was an increase in IL-10-positive T-regulatory-like cells in the mice, [a] decrease in atopic cells, and a decrease in ovalbumin IgE, the egg protein we challenged the mice with.

For the first time, we found bacterial species that protect from anaphylaxis, because a lot of focus had been on the Clostridiale species. In this particular study, [we found] that in the mice that responded after getting fecal material from patients who showed efficacy after transplantation, there was a 1000-fold increase in that bacterial species in the mice. That's a signal we would like to evaluate further.

We're hoping to evaluate Bacteroidales species alone as a consortium, but we might also be able to select some donors [based on that] We're not sure yet. We'd like to think more about it, but I think it's important to [consider] now there is a role for these bacteria in food allergy.

Fecal Transplant Sustains Peanut Allergy Protection to 12 Months

Antibiotic Pretreatment Improves FMT Response in Peanut Allergy

Abdel-Gadir A, Stephen-Victor E, Gerber GK, et al. Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy. 

Rachid R, et al. Fecal microbiome transplant in food allergy in humans and mice identifies a role for bile acid metabolites in oral tolerance. 

ClinicalTrials.gov. Evaluating the Safety and Efficacy of Oral Encapsulated Microbiota Transplantation Therapy in Peanut Allergic Patients. NCT05695261. Accessed August 12, 2026. 

https://clinicaltrials.gov/study/NCT05695261

Articles

Peanut allergy lacks therapies that sustain disease modification after discontinuation, prompting evaluation of microbiome-based approaches. Prior infant microbiome studies identified persistent dysbiosis and protective Clostridiales and Bacteroidales taxa that prevented anaphylaxis in murine models via increased IL-10–associated regulatory responses and reduced atopic parameters. Oral FMT in a phase 1 trial produced durable immunologic changes, including prolonged RORγt+ Treg expansion linked to bile acid metabolism and Bacteroides ovatus colonization, with antibiotic pretreatment improving response rates. A purified, refrigerator-stable, low-capsule MTT formulation is advancing into a randomized phase 2 trial.

Rima Rachid, MD, discusses the purified MTT formulation, phase 2 trial design, and the gut bacteria driving protection against peanut allergy.

RORγt+ regulatory T (Treg) cell expansion following fecal microbiota transplantation (FMT) persisted for up to 12 months in responders with severe 

, 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 

 "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 (

 =.0052) after FMT and remained elevated at 12 months (

 =.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 (

 =.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

Reported disclosure for Rachid includes AQUESTIVE THERAPEUTICS.

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. 

Antibiotic Pretreatment Improves FMT Response in Peanut Allergy. HCPLive. Published August 12, 2026. Accessed August 12, 2026. 

https://www.hcplive.com/view/antibiotic-pretreatment-improves-fmt-response-peanut-allergy

Videos

Rima Rachid, MD, explains how bile acid metabolism and Bacteroides colonization drive durable Treg cell induction after FMT for peanut allergy.

Antibiotic pretreatment before oral fecal microbiota transplantation (FMT) raised the peanut allergy response rate to 60% compared with 30% without pretreatment in a phase 1 trial of adults with severe 

Omalizumab is now the only FDA-approved option for peanut allergy, following the discontinuation of Palforzia oral immunotherapy on July 31, 2026, and even it lacks evidence of durable disease modification once therapy stops.

Investigators at Boston Children's Hospital tested FMT from healthy, non-allergic donors as a potential alternative in this phase 1 open-label trial.

“There is really no evidence right now that peanut oral immunotherapy can be a disease modifier, meaning that if you stop it, your disease will actually get better,” said Rima Rachid, MD, director of the Food Allergy Program and the Allergen Immunotherapy Program, Boston Children's Hospital, in an interview with 

FMT Response Rates with and without Antibiotic Pretreatment

The phase 1 open-label trial enrolled 15 adults aged 18 to 40 years with peanut allergy confirmed by reactivity to ≤ 100 mg of peanut protein on a double-blind, placebo-controlled food challenge. Participants received 36 capsules of oral encapsulated FMT from 1 of 3 screened, non-atopic donors, dosed incrementally over 1 day for most participants.¹

The first 10 participants (part A) received FMT without antibiotic pretreatment. Three of 10 (30%; 95% confidence interval [CI], 6.7%-65.3%) achieved a threshold increase to 300 mg or 600 mg of peanut protein at 1 or 4 months.

An additional 5 participants (part B) received oral vancomycin, neomycin, and metronidazole for 4 days before FMT. In total, 3 of 5 (60%; 95% CI, 14.7%-94.7%) achieved the same efficacy threshold. Overall, 6 of 15 participants (40%; 95% CI, 16.3%-67.7%) responded after a single FMT dose, with the response persisting at 4 months in all 6; 5 of the 6 responders were male, compared with 2 of 9 nonresponders (

FMT was well tolerated across the 15 participants. Three adverse events in grades 1 and 2 occurred, consisting of fatigue, diarrhea, nausea, abdominal pain, dizziness, and headache, all resolving within 12 to 48 hours. No grade 3 or higher events occurred, and no allergic reactions were attributed to FMT administration.¹

Sex-Based Response Differences in FMT for Peanut Allergy

Rachid said that she cannot yet jump to any conclusions about the apparent sex-based difference in response. She just noted it was “interesting as an observation.”

“We will need larger studies to see if there are indeed sex differences,” she said. “It’s too early to be certain. The larger studies will require a much larger number of patients… probably 1 donor per 20 patients. This is really scratching the tip of the iceberg. In this particular study, it is showing us a very promising signal, but as usual in research, it will bring a lot of questions once we have the data.”

Boston Children's Hospital. How 'good' bacteria from fecal transplants reduce peanut allergy. Published August 5, 2026. Accessed August 11, 2026. 

medicalxpress.com/news/2026-08-good-bacteria-fecal-transplants-peanut.html

HCPLive. Fecal Microbiota Transplant Boosts Peanut Tolerance in Phase 1 Trial. Published August 11, 2026. Accessed August 11, 2026. 

hcplive.com/view/fecal-microbiota-transplant-boosts-peanut-tolerance-phase-1-trial

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

Rima Rachid, MD, discussed why antibiotic pretreatment before fecal microbiota transplantation may improve peanut allergy response rates.