| Literature DB >> 31235962 |
Azza Abdel-Gadir1,2, Emmanuel Stephen-Victor1,2, Georg K Gerber3, Magali Noval Rivas4, Sen Wang1,2, Hani Harb1,2, Leighanne Wang1, Ning Li3, Elena Crestani1,2, Sara Spielman1, William Secor1, Heather Biehl1, Nicholas DiBenedetto3, Xiaoxi Dong3, Dale T Umetsu5, Lynn Bry3, Rima Rachid6,7, Talal A Chatila8,9.
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.Entities:
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Year: 2019 PMID： 31235962 PMCID： PMC6677395 DOI： 10.1038/s41591-019-0461-z
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440