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Edited* by Dan R. Littman, New York University Medical Center, New York, NY, and approved August 5, 2014 (received for review June 25, 2014)
Significance
The prevalence of food allergy is rising at an alarming rate; the US Centers for Disease Control and Prevention documented an 18% increase among children in the United States between 1997 and 2007. Twenty-first century environmental interventions are implicated by this dramatic generational increase. In this report we examine how alterations in the trillions of commensal bacteria that normally populate the gastrointestinal tract influence allergic responses to food. We identify a bacterial community that protects against sensitization and describe the mechanism by which these bacteria regulate epithelial permeability to food allergens. Our data support the development of novel adjunctive probiotic therapies to potentiate the induction of tolerance to dietary allergens.
Abstract
Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.
Footnotes
↵1A.T.S. and T.F. contributed equally to this work.
- ↵2To whom correspondence should be addressed. Email: cnagler{at}bsd.uchicago.edu.
Author contributions: A.T.S., T.F., P.T., B.R.T., D.A.A., Y.-X.F., and C.R.N. designed research; A.T.S., T.F., P.T., J.Q., M.Y.T., G.-Y.S., S.C., B.R.T., and D.A.A. performed research; K.M., S.K.M., D.A.A., L.Z., E.B.C., and Y.-X.F. contributed new reagents/analytic tools; A.T.S., T.F., P.T., J.Q., M.Y.T., S.C., D.A.A., and C.R.N. analyzed data; and A.T.S., T.F., and C.R.N. wrote the paper.
Conflict of interest statement: A provisional US patent application (61/937952) was filed on February 10, 2014.
↵*This Direct Submission article had a prearranged editor.
Data deposition: The DNA sequences reported in this paper have been deposited in the MG-RAST database (project no. 7173). The Microarray data has been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (series no. GSE60039).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1412008111/-/DCSupplemental.
Commensals protect against food allergy
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