Fecal microbiome transplant in food allergy in humans and mice identifies a role for bile acid metabolites in oral tolerance

Abstract

The gut microbiome has been implicated in the pathogenesis of food allergy (FA), prompting microbiome-focused interventions. We evaluated, in a phase 1 open-label trial (NCT02960074), the safety and efficacy of oral encapsulated fecal microbiome transplantation (FMT) in 15 adults with peanut allergies. An increase in the peanut reactivity threshold was noted in 3 of 10 participants not pretreated with antibiotics and 3 of 5 participants pretreated with antibiotics, without safety issues. In responders, FMT increased tolerogenic RORγt + regulatory T cells (T reg cells) and decreased T helper 2 cells (T H 2 cells). Mice transplanted with the microbiomes of post-FMT responders were protected from FA in association with increased RORγt + T reg cell percentages and increased colonization with members of the gut Bacteroides . In both humans and mice, protection by FMT was associated with increased bile acid metabolites. Deletion of a bile salt hydrolase in a candidate protective Bacteroides abrogated FA suppression in mice. These results suggest that FMT is a safe and potentially promising therapeutic modality for treating FA.