Commensal Bacteria Protect against Food Allergen Sensitization

Stefka, AT et al  Commensal bacteria protect against food allergen sensitization.  2014 PNAS USA 111, 13145-13150.

From Left to Right: Cathy Nagler, Andrew Stefka and Taylor Feehley

From Left to Right: Cathy Nagler, Andrew Stefka and Taylor Feehley

The prevalence of life-threatening anaphylactic responses to food is rising at an alarming rate in many parts of the world. It is increasingly clear that 21st century environmental interventions, including widespread antibiotic use, consumption of a high fat/low fiber Western diet, elimination of previously common enteropathogens (including helminthic parasites), reduced exposure to infectious disease, Caesarean birth and formula feeding have perturbed mutually beneficial interactions established with our commensal microbiome over millions of years of co-evolution. We have proposed that the resulting environmentally induced commensal dysbiosis promotes sensitization to food antigens in genetically susceptible individuals. The mechanisms by which changes in the composition of the intestinal microbiota regulate allergic responses to food have, however, been poorly understood. In this report we used murine models developed in our laboratory to demonstrate that sensitization to a food allergen is enhanced in mice that have been treated by neonatal antibiotic administration (Abx) or are devoid of commensal microbes (germ free). By selectively colonizing germ free mice we show that the allergy-protective capacity is contained within the Clostridia, a class of anaerobic spore-forming Firmicutes that reside in close proximity to the intestinal epithelium. Reintroduction of a Clostridia-containing microbiota to Abx-treated mice blocks sensitization to a food allergen. Microarray analysis of intestinal epithelial cells isolated from gnotobiotic mice helped to identify a novel innate mechanism by which Clostridia protect against sensitization to dietary antigens. Defects in intestinal permeability have been implicated in aberrant allergic responses to food, but the mechanisms governing uptake of dietary antigen have not been clear. We found that Clostridia colonization induces the production of the barrier protective cytokine IL-22 by both innate lymphoid cells and T cells in the colonic lamina propria. IL-22 acts to reduce uptake of orally administered dietary antigen into the systemic circulation, contributing to protection against sensitization. Allergen specific desensitization protocols are already showing promise in clinical trials. Our data suggest that pairing Clostridia enrichment of the gut microbiota with these tolerance-inducing regimens may potentiate antigen specific tolerance to prevent or treat food allergy.
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