Microbial Regulation of IgE Production in Early Life
Poster Feb 21, 2015
Ana B Blazquez, Jeremiah J Faith, Hugh A Sampson, M Cecilia Berin
Rationale: Changes in gastrointestinal microbiota have been suggested to drive the increasing prevalence of food allergy. Our aim was to determine the impact of mouse and human intestinal microbiota on modulation of allergic parameters including IgE.
Methods: C57BL/6 mice were treated with antibiotics (ABX) for 4 weeks. Germ-free (GF) mice were colonized with fecal microbiota from a healthy pediatric donor. Total serum IgE, IgA, and IgG were analyzed by ELISA, blood eosinophils and basophils by flow cytometry, and cytokine expression in Peyer’s patches (PP) by qPCR.
Results: ABX treatment immediately after weaning induced a significant increase in total serum IgE (45.6±10.5 ng/ml (ABX) vs 12.2±2.8 ng/ml (control), and surface IgE on basophils (4377±1371 MFI (ABX) vs 1139±666 (Control)). The levels of other isotypes were unchanged. Circulating eosinophils were also significantly increased (2.37±0.83% (ABX) vs 1.42±0.25% (control)). IL-4 was significantly upregulated in the PP after ABX-treatment of young mice. Susceptibility of IgE and eosinophils to modulation by ABX was rapidly lost, and was not observed in 5 week old mice. GF-mice had progressively increasing levels of IgE with age (187±75 ng/ml at 8 weeks and 623±131 ng/ml at 12 weeks). Colonization with human microbiota at 4 or 8 weeks of age significantly suppressed IgE as measured 4 weeks later (77.75±38.60 and 205.5±148.3 ng/ml).
Conclusions: In mice there is an early-life window of antibiotic exposure that leads to elevated IgE and other allergic parameters. Transfer of human microbiota to germ-free mice suppresses IgE and offers a unique model system to study regulatory activity of human microbiota.