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Commensal bacteria protect against food allergen sensitization

Stefka, Andrew T. and Feehley, Taylor and Tripathi, Prabhanshu and Qiu, Ju and McCoy, Kathy and Mazmanian, Sarkis K. and Tjota, Melissa Y. and Seo, Goo-Young and Cao, Severine and Theriault, Betty R. and Antonopoulos, Dionysios A. and Zhou, Liang and Chang, Eugene B. and Fu, Yang-Xin and Nagler, Cathryn R. (2014) Commensal bacteria protect against food allergen sensitization. Proceedings of the National Academy of Sciences of the United States of America, 111 (36). pp. 13145-13150. ISSN 0027-8424. PMCID PMC4246970.

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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.

Item Type:Article
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URLURL TypeDescription Information CentralArticle
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2014 National Academy of Sciences. Edited by Dan R. Littman, New York University Medical Center, New York, NY, and approved August 5, 2014 (received for review June 25, 2014). Published online before print August 25, 2014, doi: 10.1073/pnas.1412008111. We thank the staff of The University of Chicago Gnotobiotic Research Animal Facility for their expert technical assistance; T. Karrison (The University of Chicago Biostatistics Core) for advice on statistical analysis; S. Chervonsky and other colleagues for critical review of the manuscript; andW. Ouyang (Genentech) for providing neutralizing antibody to IL-22 (8E11), its isotype control, and an IL-22-Fc fusion protein for this study. This work was supported by Food Allergy Research and Education; a gift from the Bunning family; US National Institutes of Health Grants AI106302 (to C.R.N.), DK078938 (to S.K.M.), AI089954 (to L.Z.), AI091962 (to L.Z.), and T32AI007090-33 (to T.F.); and University of Chicago Digestive Diseases Research Core Center Grant DK42086. 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, (series no. GSE60039). This article contains supporting information online at
Funding AgencyGrant Number
Food Allergy Research and EducationUNSPECIFIED
Bunning familyUNSPECIFIED
NIH Predoctoral FellowshipT32AI007090-33
Subject Keywords:microbiome; barrier; IL-22
Issue or Number:36
PubMed Central ID:PMC4246970
Record Number:CaltechAUTHORS:20140825-224741284
Persistent URL:
Official Citation:Andrew T. Stefka, Taylor Feehley, Prabhanshu Tripathi, Ju Qiu, Kathy McCoy, Sarkis K. Mazmanian, Melissa Y. Tjota, Goo-Young Seo, Severine Cao, Betty R. Theriault, Dionysios A. Antonopoulos, Liang Zhou, Eugene B. Chang, Yang-Xin Fu, and Cathryn R. Nagler Commensal bacteria protect against food allergen sensitization PNAS 2014 111 (36) 13145-13150; published ahead of print August 25, 2014, doi:10.1073/pnas.1412008111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:48879
Deposited By: George Porter
Deposited On:26 Aug 2014 15:06
Last Modified:03 Oct 2019 07:08

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