Gut microbiome therapy shows early promise for peanut allergy

Clinical takeaway: Fecal microbiome transplantation remains investigational and is not ready for clinical use, but these findings support the gut microbiome as a potential therapeutic target for food allergy. Future microbiome-based therapies, such as defined bacterial consortia, may eventually offer an alternative to treatments that require ongoing maintenance.

Current food allergy treatments can reduce the risk of reactions but generally require continued therapy, and protection often wanes after treatment stops. A small phase 1 study suggests that altering the gut microbiome may help restore immune tolerance to peanut in adults with severe peanut allergy, raising the possibility of a longer-lasting treatment approach.

Researchers evaluated oral encapsulated fecal microbiome transplantation (FMT) in 15 young adults with severe peanut allergy. Participants received a single treatment consisting of frozen oral capsules containing donor gut microbes. Ten participants received FMT alone, while five received antibiotics beforehand to improve donor bacterial engraftment.

Six participants met the study's response criteria, with 3 of 10 responding without antibiotics and three of five responding after antibiotic pretreatment. Responders tolerated substantially more peanut during oral food challenge testing four months after treatment, in some cases increasing from reactions to trace exposures to tolerating the equivalent of more than four peanuts. No major safety concerns were identified.

The investigators also identified a possible mechanism underlying treatment response. Responders showed increased colonization with Bacteroides species, along with higher levels of bile acid metabolites, expansion of regulatory T cells that promote immune tolerance, and reduced type 2 inflammatory responses. Parallel experiments in mice supported these findings and suggested that bacterial metabolism of bile acids may play a key role in restoring oral tolerance.

Although the study was small, open-label, and designed primarily to assess safety, it provides the first clinical evidence that microbiome-based therapy may modify food allergy rather than simply suppress allergic reactions. Ongoing studies are evaluating more standardized formulations containing purified microbes, which could ultimately prove more practical than FMT.

"Knowing how the bacteria restore tolerance to food in allergic individuals allows us to optimize the therapy for more effective outcomes," said Talal Chatila, MD, director of translational immunology at Boston Children's Hospital.

Source: Rachid R, et al. (2026 Aug 5) Sci Transl Med. Fecal microbiome transplant in food allergy in humans and mice identifies a role for bile acid metabolites in oral tolerance