Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31235962.
- Also identified by DOI 10.1038/s41591-019-0461-z and PMC identifier 6677395.
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Abstract
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.
Medical subject headings
- Food Hypersensitivity
- Gastrointestinal Microbiome
- Myeloid Differentiation Factor 88
- Nuclear Receptor Subfamily 1, Group F, Member 3
- T-Lymphocytes, Regulatory