Peanut allergy 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

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

Rachid: 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.

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

Rachid: 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.

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

Rachid: 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.

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

Rachid: 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.

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

Rachid: 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.

Watch interviews with Racid here: Fecal Transplant Sustains Peanut Allergy Protection to 12 Months and Antibiotic Pretreatment Improves FMT Response in Peanut Allergy

References

1. 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. Nat Med. 2019;25(7):1164-1174. doi:10.1038/s41591-019-0461-z

2. Rachid R, 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. doi:10.1126/scitranslmed.aee3263

3. 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