There has been a striking generational increase in life-threatening food allergies in Westernized societies1,2. One hypothesis to explain this rising prevalence is that twenty-first century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early-life alterations may be particularly detrimental3,4. To better understand how commensal bacteria regulate food allergy in humans, we colonized germ-free mice with feces from healthy or cow’s milk allergic (CMA) infants5. We found that germ-free mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow’s milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transcriptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy.
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The open-source analysis software used in this study is publicly available and referenced as appropriate. Custom codes are available from the corresponding author upon request.
The data that support the findings of this study are available from the corresponding author upon request. The 16S rRNA and RNA-seq raw FastQ sequencing files were deposited into the National Center for Biotechnology Information Sequence Read Archive and are available under the accession numbers SRP130620 and SRP130644, respectively. Additional processed data reported in this study are available upon request.
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We thank the children and families for their participation in this study. We are grateful to D. Wesemann, E. Forbes-Blom, G. Nunez, M. Rothenberg, M. Alegre and J. Colson for discussion. We thank S. Wang, M. Bauer and A. Kemter for assistance with some experiments, M. Jarsulic for technical assistance with computing infrastructure, K. Hernandez for discussion of the statistical results and C. Weber for histopathological evaluation of all intestinal sections. Statistical consultation was also provided by M. Giurcanu of the University of Chicago Biostatistics Laboratory. We are grateful to B. Theriault and her staff at the University of Chicago Gnotobiotic Research Animal Facility for superb animal care and experimental support. This work was supported by the Sunshine Charitable Foundation (C.R.N.), a pilot award from the University of Chicago Institute for Translational Medicine (CTSA ULI TR000430, C.R.N.), National Institutes of Health (NIH) grants AI134923 (C.R.N.), DK42086 (D.A.A.) and an Italian Ministry of Health grant PE-2011-02348447 (R.B.C.). The Center for Research Informatics is funded by the Biological Sciences Division at the University of Chicago with additional support provided by the Institute for Translational Medicine/Clinical and Translational Award (NIH 5UL1TR002389-02), and the University of Chicago Comprehensive Cancer Center Support Grant (NIH P30CA014599). Bioinformatics analysis was performed on Gardner High-Performance Computing clusters at the Center for Research Informatics at the University of Chicago. A provisional US patent application (62/755,945) was filed on 5 November 2018.
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Current Allergy and Asthma Reports (2019)