FOXP3

Gut flora

IL-2 receptor

Transcription factor

Biology

Microbiology

Gene

Immunology

Allergy

Food allergy

T cell

Dysbiosis

Regulatory T cell

Genetics

Medicine

RAR-related orphan receptor gamma

Immune system

Nature Medicine

The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated. Therapy with Clostridiales species impacted by dysbiosis, either as a consortium or as monotherapy with Subdoligranulum variabile, suppressed FA in mice as did a separate immunomodulatory Bacteroidales consortium. Bacteriotherapy induced expression by regulatory T (Treg) cells of the transcription factor ROR-γt in a MyD88-dependent manner, which was deficient in FA infants and mice and ineffectively induced by their microbiota. Deletion of Myd88 or Rorc in Treg cells abrogated protection by bacteriotherapy. Thus, commensals activate a MyD88/ROR-γt pathway in nascent Treg cells to protect against FA, while dysbiosis impairs this regulatory response to promote disease. Bacteriotherapy using gut-derived bacteria from healthy human infants, but not infants with food allergies, suppresses food allergy symptoms in mice via induction of Foxp3 + Rorγt + regulatory T cells

Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy